The Challenges and Rewards of Breaking Paradigms in Diabetes Research

| June 1, 2015

3rd World Congress on Interventional Therapies for Type 2 Diabetes and the 2nd Diabetes Surgery Summit

An Interview with Ricardo Cohen, MD, Director, The Center for Obesity and Diabetes, Hospital Oswaldo Cruz, Sao Paulo, Brazil

Bariatric Times. 2015;12(6):18–20.


On September 28, 2015, London will host two seminal events: The 3rd World Congress on Interventional Therapies for Type 2 Diabetes and the 2nd Diabetes Surgery Summit.

Leading up to this event, Bariatric Times will feature interviews with members of the event’s leadership team—experts diabetes care and research. This month, we feature an interview with Dr. Ricardo Cohen, member of the organizing committee for the 3rd World Congress on Interventional Therapies for Type 2 Diabetes and the 2nd Diabetes Surgery Summit. Here, he discusses his work in diabetes research and participation in the first Diabetes Surgery Summit in 2007.

Dr. Cohen, can you please provide background on your interest and involvement in diabetes research.

Dr. Cohen: In 2005, Dr. Francesco Rubino published on the results of T2DM treatment with weight loss surgery in animal models. Rubino et al[1] studied duodenal-jejunal bypass (DJB), a stomach-preserving Roux-en-Y gastric bypass (RYGB) that excludes the proximal intestine, and gastrojejunostomy (GJ), which creates a shortcut for ingested nutrients without bypassing any intestine, performed in Goto-Kakizaki (GK) type 2 diabetic rats. They concluded that bypassing a short segment of proximal intestine directly ameliorates type 2 diabetes mellitus (T2DM) independently of effects on food intake, body weight, malabsorption, or nutrient delivery to the hindgut.

Months after the study by Rubino et al, I became involved in diabetes surgery. In 2005, I performed the first two human cases of DJB in the world in human patients with a mean body mass index (BMI) of 28kg/m2.[2] In those two cases, there was no relation between the delta BMI (weight going up or down) and the decrease of their HbA1c. After that, I started two trials, one with 35 patients[3] and one with 66 patients[4] with BMIs 30 to 35kg/m2 with uncontrolled diabetes who underwent RYGB.

From these pilot studies, we have the largest follow up data at six years and eight years postoperative. We intend to publish the 10-year follow up within the next two years.

At the time this research was being presented, most people believed there was a strong association between weight and diabetes, but the causes and consequences were not yet known. Through my involvement in these studies, I have seen the effects surgery can have on diabetes improvement. We’ve proved that there was no relation between the delta weight (weight going up) to diabetes improvement, so that was a proof of concept. Next, researchers needed to focus on mechanisms. We have done that more in the past decade and the progress is amazing.

What were some challenges and rewards in diabetes research?

Dr. Cohen: Diabetes surgery research proved to be a challenge initially because we were opposing current knowledge.

The German philosopher Arthur Schopenhauer stated, “All truth passes through three stages. First, it is ridiculed. Second, it is violently opposed. Third, it is accepted as being self-evident.”

I apply this to diabetes surgery research because we have experienced all of these stages. First, we were under strong opposition and ridicule. Now, we are merging with the diabetologists and the basic scientists and we see that everything points to the same thing: surgery with a good medical treatment is better than surgery alone or medical treatment alone. We have made great progress. One decade ago, us surgeons were new to diabetes. Those already involved in diabetes research spoke a language that we didn’t. I used to joke that we didn’t speak “Diabetolese.” Since then, we have been accepted into their field, learned their language, and worked together. Colleagues that I have worked with closely include Drs. David Cummings, Josep Vidal, Carl Le Roux, and Lee Kaplan. We have built good relationships and we have actually improved the way people see diabetes.

Today, we encourage people to view the algorithm for T2DM management to include surgery plus medical treatment and not just medical treatment alone or surgery alone.

If we continue our work together and make progress in changing the algorithm worldwide, we can achieve better outcomes for our patients.

What about your involvement in the 1st World Congress and DSS? Can you tell us about that?

Dr. Cohen: I was involved in the 1st Diabetes Surgery Summit (Rome, Italy 2007) as a faculty member. I presented data showing that surgery could be a good option for patients whose diabetes was not well controlled with medication and behavioral intervention alone.

I remember the feeling at that meeting. When I entered the large lecture room, I noticed that it was naturally divided with surgeons seated on side and the diabetologists and scientists seated on the other. It was funny because we set up a border, but it was unintentional; just a subconscious action. I sat close to Phil Schauer and some other surgeons. When we started the discussions, our groups were already separated and poised for debate.

Since that first meeting, I have seen the relationship change. Currently, we can speak the same language as the diabetologist/scientific community. We convene with the same ideas and strive for a common goal—better outcomes.
Back at the 1st summit, us surgeons were probably immature in our ideas because we may have thought that surgery would solve all of the problems. This idea was not correct. Since then, we have learned from and with the diabetologists and scientists.

We “played” together and by doing so we built a better team. Today, we don’t have big disagreements. What we have is fine-tuning, like on older televisions when you needed to adjust the dial to get a clear picture. We have the strong support of basic scientists who conduct research and give us some tools to understand the mechanisms and indications. The endocrinologists have become more open to surgery as an intervention as well.

What is the state of obesity and T2DM in Brazil and surrounding countries? How does your country compare the others?

Dr. Cohen: Forty percent of the Brazilian population is overweight or obese. It is estimated that 12 million individuals have T2DM. The mean BMI of individuals with T2DM in Brazil is 29.6.kg/m2. In the United States it is 31kg/m2 and in the Asia-Pacific region it is 25kg/m2. As you can see from these numbers, the average patient with T2DM is not morbidly obese. Our purpose is to treat these patients regardless of their BMI, and data show that a good way to treat T2DM is with surgery when the best medical treatments and lifestyle modifications alone fail. We are not proposing that we operate on everyone, but rather to operate on patients who do not achieve control with medical treatment and lifestyle modification alone.

Here in Brazil the Federal Council of Medicine, which is like the National Institutes of Health (NIH) in the United States, is very close to changing the algorithm for T2DM to include diabetes surgery free from the tight chains of BMI.Currently, it is the same as the NIH guidelines

When this change is official, it will make Brazil the first country with a large volume of bariatric/metabolic surgery(90,000 cases/year) to do so. This is very exciting and we are trying to contaminate everybody with this excitement and spur similar changes across the globe.

Dr. Cohen, do you think we need new guidelines? How might the consensus in September 2015 impact this?

Dr. Cohen: Further explanation can be found in the article I co-wrote with Dr. David Cummings titled, Beyond BMI: The Need for New Guidelines Governing the Use of Bariatric and Metabolic Surgery, published in Lancet in February 2014. We need new guidelines because most of the patients are not morbidly obese and many are dying because of diseases that are secondary to T2DM, mainly from cardiovascular events.

We are strongly working to convince the medical community and the authorities that we need a change. I think we are on the right path to really consolidate the role of surgery in the armentarium for treating T2DM. That is the main purpose of the DSS in September 2015—to merge what we think with what they (diabetologists and scientists) think and build some new guidelines for treating patients with T2DM.
The consensus from the DSS will answer questions regarding patient eligibility. We did this already in Brazil and we’re ready to be approved. I think with the DSS and World congress, we are going to reach the goal of building the best guidelines for treating our patients, customized for certain regions.

The proposal of new guidelines will be a real game changer, as it will get the medical community, legislation, and public to start viewing surgery as a powerful tool to treat uncontrolled diabetic patients. Surgery is not a miracle, but when used with medicine and lifestyle interventions, it results in much better results than lifestyle alone or medication alone.

Tell us about the areas of research in which you are currently involved? Will you be presenting results at the DSS and World Congress?

Dr. Cohen: I am involved in running a few randomized, controlled trials (RCTs). I believe on topic of research—surgery plus medical treatment versus medical treatment alone in end organ damage (microvascular complications)—is a potential game changer. Our primary results show end-stage organ damage, including diabetic kidney disease, retina disease, and neuropathy are better controlled with surgery and medical treatment versus medical treatment alone. Now, medicine alone is considered the very best treatment with glucagon-like peptide-1 (GLP-1) analogs, dipeptidyl peptidase-IV (DPPIV) inhibitors, sodium- glucose cotransporter 2 (SGLT2) inhibitors, and new insulin analogs. Even though the medical arm produces reason able glycemic control in the patient, we are finding that we achieve better end organ damage outcomes with surgery. This is very exciting as end-stage organ damage is caused by progressing diabetes. Diabetes is the biggest cause of dialysis and kidney failure in the world and also the primary cause of blindness. So, if we can prove that by treating T2DM with surgery, medication, and lifestyle intervention we can decrease the number of kidney failures, retina damage, and amputations, it will be a real game changer.

Another area of research is cardiovascular outcomes after surgery compared to medical intervention. I believe this is a difficult subject to tackle, but it is a priority.
The meeting will also include a current literature review of the state of the art of metabolic procedure outcomes, long-term outcomes. Regional meetings will also take place. I’m organizing a Latin American satellite meeting on the problems of our neighbors Argentina, Chile, and others, to try to support them in changing their guidelines based on the consensus.

The DSS and World Congress will to try to shed light to all health authorities around the world to those who need most treatment for their diabetes. The meetings will also hopefully raise awareness, allowing us to move forward to get the best treatment for the patients.

What is your hope for the meetings in September? Do you think surgeons, diabetologists, and scientists will sit together this time?

Dr. Cohen: I believe the two meetings will continue to reinforce that fact that surgery along with medication and lifestyle intervention improves or resolves T2DM.
Yes, I think we are going to be mixed together and discussing with the same purpose, which will represent a huge advance from the previous meetings.

It’s comfortable for all of us to speak about metabolic surgery today. Before, we were really trying to destroy old concepts and break paradigms, which is very tough. I’m pleasantly surprised with the progress we have all made in the last decade and the DSS-2 and World Congress will further advance that progress. The meetings will gather all of the experts in diabetes from around the world and provide a venue for their discussions and advancements. We’re going to learn a lot!

For more information, visit http://www.wcitt2d.org/. Register by July 1, 2015 to receive the “early bird” rate. For group registration (10 participants and more), please contact the registration department at reg_wcidt15@kenes.com.

References
1.    Rubino F, Forgione A, Cummings DE, et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg. 2006;244(5):741–749.]
2.    Cohen RV, Schiavon CA, Pinheiro JS, Correa JL, Rubino F. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22–34 kg/m2: a report of 2 cases. Surg Obes Relat Dis. 2007;3(2):195–197.
3.    Cohen RV, Caravatto PP, Correa JL, et al. Glycemic control after stomach-sparing duodenal-jejunal bypass surgery in diabetic patients with low body mass index. Surg Obes Relat Dis. 2012;8(4): 375–380.
4.    Cohen, RV, Pinheiro JC, Schiavon CA, et al. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care. 2012;35(7): 1420–1428.

Funding: No funding was provided in the preparation of this manuscript.

Financial disclosures: The author reports no conflicts of interest relevant to the content of this article.

Category: Interviews, Past Articles

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