Changing Paradigms with Metabolic Surgery Research

| November 1, 2015

Dr. Ricardo Cohen is the Director of The Center for Obesity and Diabetes at Oswaldo Cruz German Hospital in Sao Paulo, Brazil. He is also former President of the Brazilian Society for Bariatric and Metabolic Surgery. Dr. Cohen is a member of the Editorial Board for Surgery for Obesity and Related Diseases, Advisory Editor for Obesity Surgery, and Associate Editor for three other medical journals. He has edited nine books in laparoscopic and diabetes surgery. He has authored more than 100 scientific papers, editorials, textbook chapters, and video productions. Dr. Cohen is also a frequently invited speaker for more than 700 regional, national, and international lectures on the subject of obesity surgery and laparoscopic surgery. Dr. Cohen was also a member of the organizing committee for the 3rd World Congress on Interventional Therapies for Type 2 Diabetes and the 2nd Diabetes Surgery Summit, which took place September 28, 2015.


This column is dedicated to featuring accredited bariatric centers around the world, with a focus on their facilities, staff, statistics, processes, technology, and patient care.

Column Editor: George L. Blackburn, MD, PhD, FACS, FASMBS
S. Daniel Abraham Professor of Nutrition; Associate Director, Division of Nutrition Harvard Medical School; Director, Center for the Study of Nutrition Medicine, Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts

Column Editor: Daniel B. Jones, MD, MS, FACS
Professor of Surgery, Harvard Medical School, Vice Chair, Beth Israel Deaconess Medical Center, Boston, Massachusetts

A Message from the Column Editors
Dear Readers of Bariatric Times:
Bariatric surgery has many leaders who have shaped the field by their discoveries, teaching, and stewardship. In this column, we invite leaders to tell us about their most significant accomplishment(s). Here, we will hear from leaders about their visions, hurdles, collaborations, and, ultimately, what impact their accomplishments have had on the field of bariatric surgery. We will also learn how they set goals and have turned ideas into reality, as well as what was anticipated and what was not expected throughout their journeys.
We are very excited about this project and hope it will help to inspire the next generation of leaders as they evaluate new devices and technology and consider novel procedures and treatments in an era of cost containment. We hope you enjoy these stories.

Sincerely,
Drs. George L. Blackburn and Daniel B. Jones


Back in 2004, I read an article in the Annals of Surgery,[1] on weight-independent effects of rerouting food through the gastrointestinal tract over glucose homeostasis. That same year, during the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES), I was chatting with Dr. Bernard D’Allemagne, an old friend of mine. He convinced me to meet Dr. Francesco Rubino, and said he was “doing the same stuff that I was doing,” but in animals. That name rang a bell and I remembered that he was the first author of the article in the Annals of Surgery that got my attention. I met Dr. Rubino at that meeting and we developed a true combination of friendship (despite his lack of knowledge about soccer as a “good Italian”) and a strong scientific collaboration on the potential surgical treatment of type 2 diabetes mellitus (T2DM).

As soon as I returned to Sao Paulo, Brazil, I designed two protocols. One examined Roux-en-Y gastric bypass (RYGB) in patients with body mass indices (BMIs) between 30 and 35kg/m2. The second protocol was a pilot study that mimicked Francesco’s work with Goto-Kakizaki rats.[1]

In mid 2005, I performed the first two duodenal jejunal bypass (DJB) procedures in nonobese patients (mean BMI of 28kg/m2) with T2DM.[2] To my knowledge, these were the first operation performed under an Institutional Review Board (IRB) protocol approved to treat T2DM in a nonobese patient population.

After nine months of follow up, we found no relation between the patients’ delta BMI (weight going up or down) and the decrease of their hemoglobin A1c (HbA1c). One of the patients had insulin withdrawn 60 days after the operation and both patients were under glycemic control. I have seen both of these patients for more than 10 years now and they are still under metabolic control with much less medication than at baseline.
Since the outcomes from that initial study were good, we went on to be approved for two more IRB protocols,[3,4] one with 35 patients[3] and one with 66 patients[4] with BMIs 30 to 35kg/m2 with uncontrolled diabetes who underwent RYGB. The results were exciting. At six years follow up, 88 percent of patients reported HbA1c below 6.5% with less or no medication compared to baseline.

In 2006 and 2007, the thought that T2DM may be an intestinal and operable disease was almost heretical. In 2007, at the first Diabetes Surgery Summit (DSS-1) in Rome, Italy,[5] I presented these first pilot cases and the interim results of the DJB and RYGB in BMIs below 35kg/m2. I found that the majority of the medical community did not accept the outcomes and the idea that bariatric surgery could be used to treat T2DM in nonobese patient populations. Actually, I don’t think we (the surgical group examining GI surgery for T2DM) fully understood the mechanisms.

During the DSS-1, it was evident that surgeons and diabetologists were speaking different languages. We needed to dive into T2DM—its pathophysiology, treatment options, and complications—and we needed to fluently speak and understand a new language for surgeons, ”diabetolese.” Endocrinologists needed to keep their eyes open to this new discipline that was about to be founded—metabolic or diabetes surgery.
It is very difficult to change paradigms and that is what happened when we began to talk about metabolic surgery, which was later defined as any GI tract procedure that may lead to diabetes control initially through weight-independent mechanisms.[6]

Improving T2DM through bariatric surgery was a common observation and surgeons, myself included, used to be proud to discharge patients right after surgery without antidiabetic agents, even insulin. I felt defeated if I did not discharge a patient without diabtetes medication. Back then, I was far from understanding what was behind the devastating disease of T2DM. I realized that an association between endocrinologists, surgeons, and basic scientists was mandatory.

Since diving into diabetes surgery research, I have learned a lot from many friends around the world. I’ve established strong friendships and scientific collaborations with Drs. Phil Schauer, Francesco Rubino, David Cummings, Carel le Roux, and Lee Kaplan. I like to call them “the family.” I’ve also developed a good partnership with Dr. Samuel Klein, Director of the Center for Human Nutrition at Washington University’s School of Medicine in St Louis, Missouri. Although sometimes we do not agree, I have learned to take advantage of Dr. Klein’s ideas that provide counterbalance to mine.[7]

I continued to move forward with the concept of metabolic surgery. During 2010 and 2011, my group started a new protocol on the endoscopic duodenal liner[8] that showed good glycemic and metabolic control with virtually no weight loss in one year of follow up. This was more good news in metabolic surgery research.

It became apparent that there was a reasonable amount of patients who were not being offered a good tool for diabetes improvement in the event medical treatment failed. Thus began the crusade to show the medical community that BMI should not be the primary tool to qualify patients with uncontrolled diabetes for metabolic surgery. It has been a tireless fight, but I believe that we have made much progress.[9]

After humongous efforts made by the the Brazilian Society for Bariatric and Metabolic Surgery along with the Societies of Diabetes, Endocrinlogy, the Brazilian College of Surgeons and the College for Digestive Surgery, the Federal Council of Medicine, which is analogous to the National Institutes of Health (NIH) in the United States, is considering changing the algorithm for T2DM to include metabolic surgery, freeing us from the tight chains of BMI, based on a Metabolic Risk Score developed and agreed by the involved societies. This is a dream that is close to coming true.

When I reflect on the last 10 to 12 years of my career, one message in particular stands out. Initially, when I presented the outcomes of metabolic surgery, some people called me crazy. In 2009, after I presented data on low BMI metabolic surgery, I heard from Dr. John Buse, a prominent North American diabetologist. He told me that “being crazy does not necessarily mean that you are wrong.” Coming from a very skeptical endocrinologist, I took that as a compliment.

Metabolic surgery is an evolving field that has become more established and mature in the past 10 years. To further progress, we need to prove the effects of metabolic surgery beyond glycemic control. The Swedish Obese Subjects Study[10] has given us good prospective longitudinal long-term follow up data. Randomized controlled trials (RCT) by Schauer et al[11] and Mingrone et al[12] concluded that bariatric surgery is more effective for T2DM treatment than both conventional and intense medical therapy alone. Now, I believe the we should focus more efforts on researching the role of surgery for treating diabetes-related end-stage organ damage. I am currently involved in an RCT comparing RYGB to the best medical treatment for end-stage organ damage. The results of the trial will be out soon.

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. The evolution of metabolic surgery has progressed a lot in the last decade and I am proud to have been a part of it.

References
1.    Rubino F, Marescaux J. Effect of duodenal-jejunal exclusion in a non-obese animal model of type 2 diabetes: a new perspective for an old disease. Ann Surg. 2004;239: 1–112.
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.
5.    Rubino F, Kaplan LM, Schauer PR, et al. Diabetes Surgery Summit consensus conference: recommendations for the evaluation and use of gastrointestinal surgery to treat type 2 diabetes mellitus. Ann Surg. 2010;251:399–405.
6.    Rubino F, Cummings DE. The coming age of metabolic surgery Nat Rev Endocrinol. 2012;8(12):702–704.
7.    Klein S, Fabbrini E, Patterson BW, et al. Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes. Obesity (Silver Spring). 2012;20: 1266–1272.
8.    Cohen R, Neto M; Correa JL et al. A pilot study of the duodenal jejunal bypass liner in low BMI type 2 diabetes. J Clin Endocrinol Metab. 2013;98:E279–282.
9.    Cummings DE, Cohen, RV. Beyond BMI: the need for new guidelines governing the use of bariatric and metabolic surgery. Lancet Diabetes Endocrinol. 2014;2:175–181.
10.    Sjöström, L, Lindroos, AK, Peltonen, M et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med. 2004; 351: 2683–2693.
11.    Schauer PR, Kashyap SR, Wolski K, et al. Bariatric surgery vs. intensive medical therapy in obese patients with diabetes. N Engl J Med. 2012;366:1567–1576.
12.    Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366:1577–1585.

Funding: No funding was provided.

Financial Disclosures: The author reports receiving research grants from GI Dynamics (USA), Covidien Brazil and USA, Johnson and Johnson Medical, Brazil and Oswaldo Cruz German Hospital Biosciences Insitute, Brazil.

Author affiliation: Dr. Cohen is Director, The Center for Obesity and Diabetes, Oswaldo Cruz German Hospital, Sao Paulo, Brazil.

Category: Past Articles, The History of Bariatric Surgery

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