Bariatric Times. 2012;9(2):10–19
During the 28th Annual Meeting of the American Society for Metabolic and Bariatric Surgery (ASMBS), in Orlando, Florida, June 12 to 17, 2011, Dr. Phil Schauer moderated a panel debate entitled, “Metabolic Surgery for Diabetes: Which Operation is Most Suitable for Diabetic Patients.” In this Group Symposium, the four panel members, Drs. Jaime Ponce, Ricardo Cohen, Vivek Prachand, and Michel Gagner, presented their procedures of choice in operating on patients with diabetes and defended their positions through research and personal case examples. In this article, these panel members provide a synopsis of their presentations.
POSITION 1: GASTRIC BANDING is an Ideal Operation for Diabetes
Jaime Ponce MD, FACS, FASMBS
Dr. Ponce is the Medical Director for the Bariatric Surgery program at Hamilton Medical Center, Dalton, Georgia and Memorial Hospital, Chattanooga, Tennessee. He is the Chair of the ASMBS Insurance Committee, Vice-President of the ASMBS Tennessee State Chapter, and President-Elect of the ASMBS.
Co-Author: Brooke Lindsey, RN, CBN
Ms. Lindsey is the Bariatric Clinical Coordinator for Dalton Surgical Group in Dalton, Georgia.
Funding: No funding was provided in the preparation of this article.
Financial disclosures: Dr. Ponce has been a consultant, proctor, and faculty member and has received research support from Allergan and Ethicon Endosurgery, Inc. Ms. Lindsey reports no conflicts of interest relevant to the content of this article.
The Diabesity Problem
Diabetes now affects nearly 24 million people in the United States, an increase of more than three million in approximately two years, according to 2007 prevalence data estimates released by the Centers for Disease Control and Prevention (CDC). This means that nearly eight percent of the United States population has diabetes.
In addition to the 24 million with diabetes, another 57 million people are estimated to have pre-diabetes. Also, according to the CDC, more than 30 percent of the United States population is obese, with approximately 4 to 5 percent being obese with diabetes: these individuals can potentially benefit from metabolic bariatric surgery.
The Dixon study is the first randomized study that compares medical versus surgical therapy for type 2 diabetes mellitus (T2DM). This study included patients with obesity class I (body mass index [BMI 30–34.9kg/m2]) and obesity class 2 (BMI 35–39.9 kg/m2) who had T2DM for less than two-years duration, and the results showed a significant difference in resolution (13% vs. 73%) favoring the surgical treatment. The resolution was very dependent on weight loss, and there was significant evidence that for moderate obesity, laparoscopic adjustable gastric banding (LAGB) can provide significant weight loss with improvement and resolution of diabetes and metabolic syndrome.
According to the latest systematic review of the literature by Buchwald et al, published in the American Journal of Medicine, diabetes resolution was greatest for patients who underwent gastric bypass (70.9%) compared to LAGB (58.3%), with two years or more of follow-up data. Two factors can be identified that make this difference. First, the data showed a difference in weight loss with both procedures, with bypass having 63 percent excess weight loss (EWL) versus 49 percent in band procedures after more than two years of follow up. Better weight loss has been shown to be a factor that influences better diabetes resolution. In my own series, patients with LAGB that had better weight loss had significantly better diabetes resolution rate, a finding that O’Brien et al have confirmed as well. Second, it has been observed that the manifestations of T2DM can totally clear within days after gastric bypass in about 30 percent of the patients, according to Schauer’s experience, before there is any significant weight loss and after the immediate effect of postoperative starvation on the blood glucose level has dissipated. This finding would suggest that changes in the gut hormonal milieu after bypass of the distal stomach, duodenum, and proximal jejunum can influence the mechanism of T2DM; changes that do not exist in the LAGB procedure. Substantiation of this hypothesis comes from the studies of Rubino, who demonstrated that a bypass of the duodenum and upper jejunum in lean diabetic rats would return them to euglycemia, even though they maintained normal weight.
Other evidence of significant improvement of T2DM after banding includes a study by Dixon et al which demonstrated remission of T2DM in 64 percent of patients and showed that the predictors of remission were weight loss and duration of diabetes preoperatively. In a five-year study, the New York University group documented 54-percent T2DM remission in a group of band patients, showing better weight loss with resolution (57 vs. 38% EWL). In our personal experience, we have seen a significant positive difference in diabetes resolution when the diabetes is less than five-years duration and the weight loss is good. The long-term maintenance of this resolution will ultimately be associated with long-term weight loss. We showed that patients with diabetes who underwent LAGB and had resolution of T2DM in general were patients who achieved more than 45 to 50 percent EWL and had less than five years preoperative duration of diabetes. Patients with weight loss less than 25 percent and with more than five-year duration of diabetes had significantly less resolution of the disease. Better weight loss is usually achieved in patients with lower BMI (compared to those with higher BMI), and, in general, patients with diabetes lose less weight than patients with no diabetes. Our experience with the band4 and Schauer’s6 experience with the bypass have demonstrated this.
Is there an ideal candidate for LAGB?
I think the ideal candidate who can maximize the benefits of the LAGB is a patient with severe or morbid obesity in the lower BMI category, preferably not requiring insulin, who has the ability to understand the band and the eating behavior needed; has no financial, geographic, or personal barriers for adherence; and participates in an experienced and intensive gastric band follow-up program led by an experienced band surgeon. In addition, a younger patient with the ability to establish consistent exercise will have added chances for success. Of course, this is ideal for any weight loss procedure, but the band may become more dependent on some of the follow-up needs long term, which become critical for success in patients with higher BMI.
1. 2007 National Diabetes Fact Sheet. http://www.cdc.gov/diabetes/pubs/es timates07.htm#1. Access date: March 15, 2010.
2. Dixon JB, O’Brien PE, Playfair J, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial. JAMA. 2008;299(3):316–323.
3. Buchwald H, Estok R, Fahrbach K, et al. Weight and type 2 diabetes after bariatric surgery: systematic review and meta-analysis. Am J Med. 2009;122(3):248–256.e5.
4. Ponce J, Haynes B, Paynter S, et al. Effect of Lap-Band-induced weight loss on type 2 diabetes mellitus and hypertension. Obes Surg. 2004;14:1335–1342.
4. O’Brien PE, Dixon JB, Laurie C, et al. Treatment of mild to moderate obesity with laparoscopic adjustable gastric banding or an intensive medical program: a randomized trial. Ann Intern Med. 2006;144(9):625–633.
6. Schauer PR, Burguera B, Ikramuddin S, et al. Effect of laparoscopic Roux-en-Y gastric bypass on type 2 diabetes mellitus. Ann Surg. 2003;238:467–485.
7. 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;244:741–749.
8. Dixon JB, O’Brien PE. Health outcomes of severely obese type 2 diabetic subjects 1 year after laparoscopic adjustable gastric banding. Diabetes Care. 2002;25:358-363
9. Sultan S, Gupta D, Parikh M, et al. Five-year outcomes of patients with type 2 diabetes who underwent laparoscopic adjustable gastric banding. Surg Obes Relat Dis. 2010;6:373–376.
Case Examples demonstrating the effectiveness of gastric banding in the patient population with diabetes
Case #1: A 42-year-old caucasian woman with morbid obesity with a BMI of 43.4kg/m2 was diagnosed with type 2 diabetes mellitus (T2DM) three years prior to presentation. She was managed with metformin orally, average fasting glucose 120 to 130, and last glycated hemoglobin of 6.8. The patient requested a LAGB after all options were presented because both her sister and cousin had LAGB procedures with successful weight loss. The patient also felt comfortable with the risk associated with LAGB. At one-year postoperative, she lost 42 percent EWL and her glycated hemoglobin was down to 5.7. At four years postoperative, she has been able to maintain good diabetes control with a maximum weight loss of 52 percent of her excess weight.
Case #2: A 44-year-old Caucasian man with morbid obesity with a BMI of 40.5kg/m2 was diagnosed with T2DM six years prior to presentation. He was managed with two oral hypoglycemic agents and was told by his primary care physician that insulin would be needed in order to get better control of his diabetes. After extensive discussion of the alternatives and possible outcomes, he had a LAGB procedure. His glycated hemoglobin was 7.9 preoperative. At two years postoperative, he lost 44 percent of excess weight and was only taking one oral agent for diabetes control—no insulin required. His diabetes improved but is not in remission.
POSITION 2: BYPASS OPERATIONS are Ideal Operations for Diabetes
Ricardo Cohen, MD, FACS
Dr. Cohen is from The Center of Excellence for Bariatric and Metabolic Surgery, Oswaldo Cruz Hospital in Sao Paulo, Brazil. he is also the current President of the Brazilian Society for Bariatric and Metabolic Surgery.
Tarissa Petry, MD
Dr. Petry is from The Center of Excellence for Bariatric and Metabolic Surgery-Oswaldo Cruz Hospital in Sao Paulo, Brazil.
Pedro P. Caravatto, MD
Dr. Caravatto is from The Center of Excellence for Bariatric and Metabolic Surgery, Oswaldo Cruz Hospital in Sao Paulo, Brazil.
Funding: Dr. Cohen received a research grant from Covidien for the preparation of this research.
Financial disclosures: The authors report no conflicts of interest relevant to the content of this article.
Gastrointestinal (GI) bypass operations, such as the Roux-en-Y gastric bypass surgery (RYGB), biliopancreatic diversions (BPD), and duodenal jejunal bypass (DJB) with or without sleeve gastrectomy (SG), can cause complete remission of type 2 diabetes mellitus (T2DM) in 40 to 93 percent of cases, often before substantial weight loss occurs. Mounting evidence indicates that this remarkable effect results from mechanisms beyond just reductions in food intake and body weight.[2–5] Among the implicated weight-independent antidiabetes mechanisms, a role has been hypothesized for physiologic changes caused by excluding the proximal intestine from contact with ingested nutrients.[6,7]
Although weight loss is an important mechanism for T2DM control,[8,9] bypass operations have some direct antidiabetic effects, while weight loss seems to be a major player and sometimes the only player in T2DM remission after other described procedures, such as adjustable gastric banding (AGB) and SG.
Why bypass operations work
While other procedures similar to the SG struggle to fundament their mechanism of action on glucagon-like peptide-1 (GLP1) release and weight loss, the mechanisms involved in T2DM remission in GI bypass operations are multiple, weight-loss independent, and not merely related to incretin secretion.
The following are direct antidiabetic mechanisms that occur after GI bypass operations that contribute to the procedures’ ability to improve or resolve T2DM:
1. Collapse of ghrelin—this has some direct and counter regulatory actions against insulin secretion.[11,12]
2. Decreased lipotoxicity is non-weight loss related—GI bypass may decrease myocellular triglycerides and free fatty acids trafficking, thus decreasing the lipotoxic state.[2,3]
3. Changes in vagal tone of the excluded intestine—interrupting afferent vagal stimulation may increase insulin sensitivity and decrease hepatic glucose production.[4,5]
4. Intestinal gluconeogenesis after food transit rearrangement, not incretin median, would decrease hepatic glucose production.
5. Glucose transport function is decreased and glucose absorptive capacity is reduced.
6. Increased insulin sensitivity occurs secondary to changes in adipocytokine secretion, and a decrease in the inflammatory response occurs.[8,10]
7. Metabolomics—when two groups were compared, matched diet induced and surgical weight loss, in the second, decreased branched chain amino acids (BCAA) and its metabolites led to increased insulin sensitivity.
Results in patients with Morbid Obesity
In 2009, Buchwald et al shared a meta-analysis that revealed compelling data about the remission of T2DM after GI bypass surgery. After reviewing 19 studies and 4,070 patients, the authors reported 71 to 96 percent of T2DM remission. Some critiques14 may arise regarding the criteria employed to define remission in those studies, as there were no standard criteria for T2DM partial or complete remission. In early 2012, Pournaras et al from the Imperial College of London utilized the new definitions of T2DM remission (2009) where remission means A1c below 6, fasting plasma glucose below 100mg/dL, and no antidiabetics for at least one year. Although the number of complete remission after RYGB fell to 41 percent, the results are still extraordinary.
Results in patients with lower BMIs
Today, reports are increasing of GI bypass operations being performed in patients with diabetes who have low BMI.[16,17] RYGB and BPD reported in BMIs from 30kg/m2 to 35kg/m2 showed high rates according to the new strict criteria for T2D remission, ranging from 90 to 98 percent. Even in patients with lower BMIs (<30kg/m2), good results have been reported in DJB and sleeved DJB regarding glycemic control and improved ß cell function without relation to weight loss.[11,18] Employing the new criteria, 30 to 40 percent of all patients can achieve complete remission from 12 to 24 months. Longer follow up is needed, but surgery has a role in the algorithm for T2DM treatment as a primary resource or as an additional tool to reach T2DM control associated with optimized medical care.
At our facility, we have performed a collaborative study19 with a Spanish group comparing GI bypass operations and SG regarding T2DM control. The results of the study have shown that the surgical technique that excludes the duodenum (i.e., BPD, RYGB) has immediate postoperative changes in the degree of insulin resistance in patients with morbid obesity compared to those techniques that do not exclude the duodenum (i.e., SG). SG results were dependent on weight loss.
Lee et al from Taiwan compared T2DM outcomes with GI bypass procedures and SG with the same weight loss at six months postoperatively. Weight loss between both groups was similar, but T2DM remission (A1c<6.5% and FPG <100mg/dL) was 93.3 percent in the bypass group versus 34.7 percent in the SG group.
We believe bypass operations are the best options for treatment of T2DM in patients choosing to undergo weight loss surgery, primarily because these oprations effect not only weight loss changes, but also intestinal hormonal changes. Studies are needed to determine timing for the intervention (early after medical treatment failure), and if surgery should be a primary option for a selected group of diabetic patients.
1. Lee WJ, Chong K, Ser KH, et al. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch Surg. 2011;146(2):143–148.
2. Greco AV, Mingrone G, Giancaterini A, et al. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes. 2002;51(1):144–151.
3. Adami GF, Papadia F, Camerini G, et al. Magnetic resonance spectroscopy facilitates assesment of intramyocellular lipid change: a preliminary short term study following biliopancreatic diversion. Obes Surg. 2005;15:123–127.
4. D’Allesio DA, Kieffer TJ, Taborsky GJ, Havel PJ. Activation of the parasympathetic nervous system is necessary for normal meal-induced insulin secretion in rhesus macaques. JCEM. 2001;86:1253–1259.
5. Liu M, Seino S, Kirchgessner AL. Identification and characterization of glucoresponsive neurons in the enteric nervous system. J Neurosci. 1999;19(23):10305–10317.
6. Troy S, Soty M, Ribeiro L, et al. Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice. Cell Metab. 2008;8(3):201–211.
7. Stearns TA, Balakrishnan A, Tavakkolizadeh A. Impact of Roux-en-Y gastric bypass surgery on rat intestinal glucose transport. Am J Physiol Gastrointest Liver Physiol. 2009;297(5):G950–G955.
8. Clemont K, Viguerie N, Poitou C, et al. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects. FASEB J. 2004;18:1657–1669.
9. Laferrere B, Reilly D, Arias S, et al. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Sci Transl Med. 2011;3(80):80re2.
10. Cancello R, Henegar C, Viguerie N, et al. Reduction of macrophge infiltrationand chemoattractant gene expression genes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes. 2005;54:2277–2286.
11. Klein S, Fabbrini E, Patterson, et al. Moderate effect of duodenal-jejunal bypass surgery on glucose homeostasis in patients with type 2 diabetes. Obesity (Silver Spring). 2012 Jan 19 [Epub ahead of print]
12. Lee WJ, Chen CY, Cheong K, et al. Changes in postprandial gut hormones after metabolic surgery: a comparison of gastric bypass and sleeve gastrectomy. Surg Obes Relat Dis. 2011;7(6):683–690.
13. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724–1737.
14. Buse J, Caprio S, Cefalu WT, et al. How do we define cure of diabetes? Diabetes Care. 2009;32(11): 2133–2135.
15. Pournaras DJ, Aasheim ET, Søvik TT, Andrews R, Mahon D, Welbourn R, Olbers T, le Roux CW. Effect of the definition of type II diabetes remission in the evaluation of bariatric surgery for metabolic disorders. Br J Surg. 2012 Jan;99(1):100–103.
16. Cohen RV, Pinheiro JS, Correa JL, Schiavon CA. Laparoscopic Roux-en-Y gastric bypass for BMI<35kg/m2: a tailored approach. Surg Obes Rel Dis. 2006;2:401–404.
17. Geloneze B, Geloneze SR, Fiori C, et al. Surgery for nonobese type 2 diabetic patients: an interventional study with duodenal-jejunal exclusion. Obes Surg. 2009;19:1077–1083.
18. Cohen RV, Schiavon CA, Pinheiro JS, et al. Duodenal-jejunal bypass for the treatment of type 2 diabetes in patients with body mass index of 22–34kg/m2: a report of two cases. Surg Obes Rel Dis. 2007;3:195–197.
19. Garrido-Sanchez L, Murri M, Rivas-Becerra J, et al. Bypass of the duodenum improves insulin resistance much more rapidly than sleeve gastrectomy. Surg Obes Relat Dis. 2011 Mar 31. [Epub ahead of print]
Case Example demonstrating the effectiveness of bypass operations in the patient population with diabetes
A 52-year-old woman with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 31.1kg/m2 underwent a modest partial gastrectomy with Billroth I intestinal reconstruction to treat refractory peptic ulcer disease. Despite treatment with metformin 2g/day and glimepiride 2mg/day, her diabetes was inadequately controlled, with hemoglobin A1c (HbA1c) 7.5 percent and fasting plasma glucose (FPG) 154mg/dL. Ten years later, she presented with refractory alkaline reflux gastritis (a known complication of Billroth I reconstructions), which had been unresponsive to medical therapy for more than one year. Her diabetes had progressively worsened during the interim. In addition to the aforementioned medications, which were both increased to maximum doses, she was also taking maximum-dose pioglitazone. Despite these three medicines, her glycemic control worsened (HbA1c 8.7%, FPG 165mg/dL, post-oral-glucose-tolerance-test plasma glucose 269mg/dL). Her BMI had remained essentially stable, at 30.1kg/m2.
Her alkaline reflux gastritis was treated by converting the Billroth I intestinal configuration, in which bile reflux is commonplace, into a Roux-en-Y configuration, which reduces reflux and also bypasses the duodenum. This generated intestinal anatomy identical to that after a standard Roux-en-Y gasrtric bypass (RYGB). Because promoting weight loss was not an objective, however, the gastric reservoir was made ≥15 times larger than a typical functional RYGB gastric pouch, and the gastrojejunal anastomosis was designed not to restrict food passage, having a 3cm diameter instead of the usual <1cm RYGB diameter.
After mild, transient weight loss immediately following surgery, the patient described normal eating and maintained a stable body weight (64.9kg before surgery and 64.6, 64.0, and 64.8kg at 1, 3, and 6 months after surgery, respectively). Nevertheless, her diabetes quickly and durably resolved. At three days and three months postoperativey, her mean (±SD) fasting and two-hour postprandial blood glucose values (measured daily via glucometer) were 98±11 and 141±7mg/dL, respectively. At three months, her HbA1c had decreased to 6.9 percent (from 8.7% preoperatively), so glimepiride and pioglitazone were discontinued. At six months postoperatively, her HbA1c had decreased further to 5.6 percent. FPG was 102mg/dL, and maximum plasma glucose after an oral glucose tolerance test was only 115mg/dL. Because these values were no longer in the diabetic range, metformin was withdrawn. She has subsequently remained euglycemic and off all diabetes medications and without weight loss for two years.
POSITION 3: LAPAROSCOPIC BILIOPNCREATIC DIVERSION WITH OR WITHOUT DUODENAL SWITCH is an Ideal Operation for Diabetes
Vivek N. Prachand MD FACS
Dr. Prachand is Associate Professor, Section of General Surgery at the University of Chicago Medicine and Biological Sciences in Chicago, Illinois
Funding: No funding was prrovided in the preparation of this article.
Financial disclosures: Dr. Prachand reports no conflicts of interest relevant to the content of this article.
When considering the most suitable surgical option for patients with obesity and type 2 diabetes mellitus (T2DM), one needs to consider the criteria for an ideal procedure: safety, complete and prolonged T2DM remission, reduction of diabetic complications, positive impact on other metabolic conditions, significant and sustained weight loss, and substantially improved quality of life. In appropriately selected patients, the laparoscopic biliopancreatic diversion with or without duodenal switch (LBPD/DS) provides the surgeon and the patient with the highest likelihood of meeting these goals.
LBPD/DS—Questions and Concerns
A frequently mentioned concern regarding LBPD/DS is the increased perioperative risk in comparison to other bariatric procedures identified in earlier studies. More recent comparisons of the safety of LBPD/DS to Roux-en-Y gastric bypass (RYGB), however, have shown no significant differences in morbidity or mortality between the procedures when performed at centers experienced with both procedures. Another appropriate concern often raised about LBPD/DS is that of long-term nutritional deficiencies that can develop given its greater degree of malabsorption as well as the logistical difficulty encountered when attempting to maintain long-term patient follow up. Recognition and correction of preoperative nutritional deficiencies and recent publication of nutritional supplementation and repletion protocols, however, should help to address this concern. Finally, many surgeons (most whom do not regularly perform LBPD/DS) claim that LBPD/DS inevitably leads to disabling alterations in bowel habits. It is true that bowel movement frequency is increased, and that the LBPD/DS patient who eats a high-fat meal will likely experience steatorrhea (a condition mainly characterized by an increased fat discharge in the patient’s stool). With appropriate diet and use of a 100cm common channel, however, patients typically describe having 2 to 4 bowel movements per day in a predictable pattern with very rare urgency or incontinence. To provide some context, patients with ulcerative colitis who have undergone restorative proctocolectomy with ileal pouch/anal anastomosis typically have 6 to 10 bowel movements per day, yet few surgeons (and fewer patients) would argue that these patients should have permanent end ileostomies.
T2DM Improvement Versus Remission
When considering the impact of bariatric surgery on T2DM, it is important to highlight the significant qualitative difference between T2DM remission and T2DM improvement. All things being equal, it is better not to have diabetes than to have well-controlled diabetes. Modest weight loss (nonsurgical or surgical) leads to better glycemic control, but only surgery (with very rare exception) leads to complete T2DM remission, particularly when the diabetes is longstanding or severe (conversely, the greater the severity and duration of T2DM, the lower the likelihood of remission, even with significant weight loss, ostensibly due to loss of beta cell function). Furthermore, the elimination of diabetes-related medications, supplies, laboratory tests, and clinic visits substantially contributes to the cost effectiveness and value of bariatric surgery.
The majority of the current literature supports the statement that in addition to achieving greater weight loss in patients with super obesity (BMI≥50kg/m2), the likelihood of diabetes remission with LBPD/DS is significantly higher than with other bariatric procedures, even when diabetes is severe, with T2DM remission rates approaching 90 to 100 percent as opposed to 60 to 85 percent. Interestingly, this effect may in fact be independent of the magnitude of weight loss, at least in patients with super obesity. Proposed mechanisms by which diabetes is improved include caloric restriction, the hindgut hypothesis, and the foregut hypothesis. The hindgut hypothesis suggests that the expedited delivery of nutrients to the ileum causes decreased gastrointestinal motility, improvement in diabetes, and weight loss, resulting in the accentuated production of peptides produced by L cells in the distal small intestine, including glucagon-like peptide (GLP)-1, peptide YY, and oxyntomodulin, which may be responsible for these physiologic effects. The foregut hypothesis suggests that the bypass of the duodenum and proximal jejunum or the lack of food exposure to these areas of the small intestine, might be a mechanism by which improvement in glucose tolerance is achieved.
In contrast to the other bariatric procedures, LBPD/DS impacts all three of these mechanisms. Indeed, elegant physiologic studies have demonstrated altered incretin response, restoration of insulin sensitivity, increased acute insulin response to intravenous (IV) glucose, and intramyocellular lipid depletion following LBPD/DS.
In addition to leading to higher T2DM remission rates, Iaconelli et al have recently demonstrated that LBPD/DS reduces the development of diabetes complications when compared to medically managed controls, including diabetic nephropathy and probability of coronary heart disease events at 10 years after surgery. While the study was an open case-control (and nonrandomized) study, no other bariatric procedure has been shown to have this important effect.
Results in Patients with Low BMI
Currently, significant interest exists in the potential application of bariatric surgery to treat diabetes and other metabolic disorders in nonseverely obese individuals (body mass index [BMI] 25–35kg/m2), who make up the vast majority of patients with T2DM. The theoretical risks of excessive weight loss and nutritional deficiency is of major concern in this patient population, particularly so with BPD/DS.
In 2011, Scopinaro et al published a study of 30 patients who were overweight or had mildly obesity (BMI 25–35kg/m2) who underwent BPD. The authors found that none of the patients experienced excessive weight loss at 12 months postoperatively. Although there was a 100-percent rate of excellent-or-improved T2DM control 12 months postoperatiely, remission in this low-BMI population was only 30 percent as opposed to the 90-to-100 percent remission rate seen in patients with high BMI (BMI ≥35kg/m2) in other studies. These results suggest that T2DM in nonseverely obese individuals may be significantly biologically different than T2DM in individuals with severe obesity, perhaps due to the differences in relative contribution of excess adiposity to the pathophysiology of T2DM between the two groups.
While data exist proving the effectiveness of bariatric surgical procedures, particularly LBPD/DS, on T2DM in patients with BMI≥35kg/m2, the results of surgery on T2DM and other metabolic conditions may, in fact, be less robust in less obese (BMI≤35/kg/m2) patients. Therefore, we should be cautious about advocating “metabolic” rather than “bariatric” surgery in nonseverely obese patients until more data becomes available. In our practice, the BPD/DS is the procedure that we usually recommend to our diabetic patients whose BMI exceeds 50kg/m2, and strongly consider it as a reasonable option for individuals with severe, longstanding diabetes with BMI 35 to 50kg/m2. As with any bariatric procedure, this is a collaborative decision with the patient, and must take into account feasibility of follow up, vitamin adherence, and adoption of healthy eating and excercise behaviors.
1. Prachand VN, Davee RT, Alverdy JC. Duodenal switch provides superior weight loss in the super-obese (BMI ≥50 kg/m2) compared with gastric bypass. Ann Surg. 2006;244(4):611–619.
2. Søvik TT, Taha O, Aasheim ET, et al. Randomized clinical trial of laparoscopic gastric bypass versus laparoscopic duodenal switch for superobesity. Br J Surg. 2010;97(2):160–166.
3. Buchwald H, Kellogg TA, Leslie DB, Ikramuddin S. Duodenal switch operative mortality and morbidity are not impacted by body mass index. Ann Surg. 2008;248(4):541–548.
4. Prachand VN, Ward M, Alverdy JC. Duodenal switch provides superior resolution of metabolic comorbidities independent of weight loss in the super-obese (BMI≥50 kg/m2) compared with gastric bypass. J Gastrointest Surg. 2010;14(2):211–220.
5. Dorman RB, Serrot FJ, Miller CJ, et al. Case-matched outcomes in bariatric surgery for treatment of type 2 diabetes in the morbidly obese patient. Ann Surg. 2012;255(2):287–293.
6. Aasheim ET, Björkman S, Søvik TT, et al. Vitamin status after bariatric surgery: a randomized study of gastric bypass and duodenal switch. Am J Clin Nutr. 2009;90(1):15–22. Epub 2009 May 13. Erratum in: Am J Clin Nutr. 2010;91(1):239–240.
7. Guidone C, Manco M, Valera-Mora E, et al. Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes. 2006;55(7):2025–2031.
8. Adami GF, Cordera R, Camerini G, Marinari GM, Scopinaro N. Long-term normalization of insulin sensitivity following biliopancreatic diversion for obesity. Int J Obes Relat Metab Disord. 2004;28(5):671–673.
9. Iaconelli A, Panunzi S, De Gaetano A, et al. Effects of bilio-pancreatic diversion on diabetic complications: a 10-year follow-up. Diabetes Care. 2011;34(3):561–567. Epub 2011 Jan 31.
10. Scopinaro N, Adami GF, Papadia FS, et al. Effects of biliopanceratic diversion on type 2 diabetes in patients with BMI 25 to 35. Ann Surg. 2011;253(4):699–703.
Case Example demonstrating the effectiveness of duodenal switch in the patient population with diabetes
A 58-year-old Asian man with severe obesity (BMI=42kg/m2), and a 15-year history of type 2 diabetes mellitus (T2DM) was taking 140 units of insulin daily and his hemoglobin A1c (HbA1c) was 7.3 percent. He presented o the bariatric surgery clinic with hypertension, dyslipidemia, for which he was taking four medications, obstructive sleep apnea (OSA), gastroesophageal reflux disease, and gout. He was found to be an appropriate candidate for bariatric surgery and specifically requested laparoscopic duodenal switch (LDS) based on his research of the topic. After extensive discussion of the various surgical options, the decision was made to proceed with LDS. Specifically, although his body mass index (BMI) did not put him in the super-obese category (BMI≥50kg/mg2), the severity of his diabetes, hypertension, and dyslipidemia made the improved rate of remission of metabolic comorbidities seen with the LDS the preferred procedure. We extensively discussed the potential risk of excessive weight loss as well as relative disadvantages of DS, including greater risk of nutritional deficiencies. In an effort to further evaluate the likelihood of diabetes remission, a C-peptide level was obtained and was found to be 2.8ng/mL (0.9–4.3 being normal), demonstrating continued beta cell function and as such, we decided to proceed with LDS. The procedure was uneventfully performed laparoscopically, using a 60F bougie for sleeve gastrectomy (SG) beginning 5cm from the pylorus and a 100cm common channel and 150cm alimentary limb. The patient was discharged on Postoperative Day 2 (POD2). Three weeks after surgery, he had lost 26-percent of his excess body weight and was using 40 units of insulin daily. At one year postoperative, the patient’s weight had stabilized over the last four weeks at 162 pounds (BMI=25.2kg/m2), corresponding to an 88-percent excess body weight loss. He discontinued use of all diabetic medications and his fasting blood glucose was between 80 and 90. His antihypertensive regimen was halved in number of medications and dosages, and his lipid levels allowed him to discontinue the use of lipid-lowering agents. He was walking regularly and recently added resistance exercises to his regimen. He described having 3 to 6 daily bowel movements with steatorrhea once every two weeks after eating a fatty meal. Laboratory testing included albumin, vitamin A, and 25-OH vitamin D in the normal range.
POSITION 4: SLEEVE GASTRECTOMY is an Ideal Operation for Diabetes
Michel Gagner, MD, FRCSC, FACS, FASMBS, FICS, AFC (Hon.)
Dr. Gagner is Clinical Professor of Surgery, Florida International University School of Medicine, Miami, Florida.
Funding: No funding was provided in the preparation of this article.
Financial disclosures: Dr. Gagner has received honorarium from Ethicon EndoSurgery, Covidien, and W.L. Gore.
Recently, the International Diabetes Federation (IDF) published a report endorsing weight loss surgery as an accepted option in people with type 2 diabetes mellitus (T2DM) and a body mass index (BMI) of 35kg/m2 or more.1 Further, the report stated that weight loss surgery should be considered as an alternative treatment option in patients with a BMI between 30 and 35kg/m2 when diabetes cannot be adequately controlled. Individuals of non-Caucasian ethnicity (e.g., Asian, African American, Hispanic) carry an increased risk of developing diabetes, and therefore, BMI action points may be adjusted 2.5kg/m2.
It has been known for more than 50 years that some forms of gastrectomy may influence T2DM. This effect is also seen in the laparoscopic sleeve gastrectomy (SG) procedure, which harbors many clinical advantages over intestinal surgical procedures. These clinical advantages of SG are as follows: 1) is easier to perform technically compared to other procedures, 2) has lower morbidity and mortality, 3) has a shorter operating time and hospital stay, 4) has minimal effects on micronutrients, and 5) is easier to perform a reoperation for revision (Table 1).
Mechanism of Action on T2DM
Restoration of the first phase of insulin secretion and improved insulin sensitivity in patients with obesity and T2DM immediately after SG, before any food passage through the gastrointestinal tract and before any weight loss, seem to be related to ghrelin, GLP-1, and PYY hormonal changes of possible gastric origin, not meal consumption or weight change.4 A T2DM duration of 10.5 years seems to be a major cut off in the pathophysiological changes induced by SG. A “gastric” hypothesis may explain the antidiabetes effect of SG.
A very recent discovery by Kebede et al on the FFA1/GPR40, which plays a major role in the regulation of insulin secretion by fatty acids, may be the basis of why bariatric surgery is successful in reversing T2DM. After bariatric surgery, triglycerides are broken down to cholesterol and free fatty acids (FFAs). Since the release of FFAs are strongest with a duodenal switch (DS) procedure, quite good with a gastric bypass, and moderate with SG, there might be a correlation between the surgical response of reducing FFAs, and a procedure’s effect on FFA1/GPR40 receptor and insulin secretion in glucose metabolism.
Kebede et al, a team from the University of Montreal, with international collaboration, discovered that glucose stimulates FFAs (also known as GPR40) gene transcription in pancreatic b cells via increased binding of pancreas-duodenum homeobox-1 (Pdx-1) to the A-box in the HR2 region of the GPR40 promoter. Through this unique mechanism, glucose metabolism regulates the function of transcription factors in the nucleus to induce gene expression.
Christiansen et al identified that linoleic acid stimulates FFA1 receptors and insulin production as well, leading to excellent metabolic stability.
Researchers have also found profound changes of fat mass after SG and other bariatric procedures.[7,8] These changes in fat mass cause a release of triglycerides from the fat cells, triggering a large release of FFA with subsequent stimulation of the the FFA1/GPR40 receptor. This may explain the reversed phenomenon in which weight regain, re-expansion of the fat mass, and accumulation of FFA into triacylglycerol, which make less circulating FFA, would decrease the stimulation of FFA1/GPR40 receptor.
As SG grows in popularity over the years, so do the data proving its effectiveness on weight loss and T2DM improvement.
SG in patients with morbid obesity and metabolic syndrome. Hady et al performed a study that demonstrated good results in 130 patients with morbid obesity who met at least three criteria for the diagnosis of metabolic syndrome, according to the IDF. All patients underwent SG between 2007 and 2010. At one year postoperatively, the patients had a significant reduction of more than 20 BMI points (p<0.00001) and a reduction in waist circumference. None of the patients met the required five criteria for the matabolic syndrome one year postoperatively. The authors concluded that in this study, SG was easier to perform and the patients had a shorter hospital stay, and lower morbidity than with intestinal anastomotic procedures (e.g., gastric bypass, duodenal switch).
Resolution of T2DM in patients with morbid obesity is extremely similar to the effect of gastric bypass, as demonstrated by a comparative study of both cohorts in Barcelona,[11,12] demonstrating a resolution of diabetes at 85 percent in both groups in the first year. At three years postoperatively, the effect is sustained in a cohort of patients operated in India.
SG in patients with low BMIs. Lee et al concluded that SG may be less effective on T2DM in patients with obesity or moderate obesity (BMI<25kg/m2 and <35kg/m2) than on patients with morbid obesity (BMI>35kg/m2), especially if preoperative C-peptide levels preoperatively are less than 3ng/mL (14% resolution) as opposed to 6ng/mL (100% resolution). I suspect, however, that in the procedures performed during this study, the sleeve was constructed without a bougie and was too large to trigger the best antidiabetic effect, thus inadequately reducing the ghrelin cells and changing the fat mass compartment of these patients (the weight decrease on average from 31 to 25kg/m2), and mean hemoglobin A1c (HbA1C) decrease from 10.1 to 7.1 percent.
SG versus other procedures. In a study using animals, Li et al found that SG had better antidiabetic effects than a simple duodeno-jejunal bypass (a duodeno switch without sleeve gastrectomy). They also found that SG was easier to perform and resulted in less complications, shorter operative time (P<0.01), and postoperative recovery time (P<0.01) than the duodeno-jejunal bypass. The group of animals who underwent SG also showed significantly improved blood glucose levels and significantly decreased ghrelin secretion (P<0.001).
Gill et al conducted a systematic review of 27 studies analyzing a total of 673 patients. The baseline mean BMI was 47.4kg/m2 (range 31.0–53.5kg/m2). The mean percentage of excess weight loss (EWL) was 47.3 percent (range 6.3–74.6%), with a mean follow up of 13.1 months (range 3–36 months). T2DM had resolved in 66.2 percent of the patients, improved in 26.9 percent, and remained stable in 13.1 percent. The mean decrease in blood glucose and hemoglobin A1c after SG was -88.2mg/dL and -1.7 percent, respectively.
Lee et al performed the only randomized trial comparing gastric bypass (mini-gastric not Roux-en-Y) with SG. The study included 60 patients who underwent SG and were evaluated at one-year postoperatively. Remission of T2DM was achieved in 28 patients (93%) in the gastric bypass group and 14 patients (47%) in the SG group (P=.02). Unfortunately, the study had to be discarded because there was no equipoise, and the SG was not performed with a bougie (2cm from the vessels margin), resulting in an inadequate sleeve and inadequate operation. There was much more weight loss from mini-gastric bypass, which makes it suspicious, as most studies comparing both operations have demonstrated an equal weight loss at one year. This study demonstrated that T2DM resolution can be achieved without duodenal exclusion.
Chambers et al conducted a similar study comparing RYGB and SG using rats. After surgery, the rats in both groups ate less food, lost more weight, and had improved glucose parameters. The most intriguing aspect of these findings was that the two surgical procedures had such similar effects despite quite different rearrangements of the gastrointestinal system.
Nocca et al compared gastric bypass with SG. Average BMIs in the gastric bypass and SG groups were 47.9kg/m2 and 50.6kg/m2, respectively. At one year postoperatively, the average HbA1c loss in the gastric bypass and SG groups were 2,537 and 2,175, respectively. T2DM resolution (withdrawal of pharmacological treatment) in the gastric bypass and SG groups was 60 and 75.8 percent, respectively. This study demonstrated completely reversed findings from Lee et al, as the sleeve was done with an adequate bougie sizing. Reduced use of pharmacological therapy was noted in 31.42 and 15.15 percent of the gastric bypass and SG groups, respectively. Percentage EWL and BMI reduction were 56.35 and 29.75 percent, respectively, in the gastric bypass group and 60.11 and 29.80 percent, respectively, in the SG group. They concluded that during short-term follow up, the impact on regulation of HbA1c blood level after gastric bypass or SG is important. Nocca et al19 demonstrated that SG seems to be as effective as gastric bypass in managing T2DM one year postoperatively in patients with severe obesity.
Chouillard et al conducted a case-control study in 200 patients comparing Roux-en-Y gastric bypass (RYGB) and SG for the treatment of morbid obesity. They found that the morbidity rate was significantly greater in the RYGB group (20.5%) as compared to the SG group (6.5%; P<.05) and that the overall remission of T2DM was significantly better in the RYGB group (P<.05). However, the percentage of EWL and resolution of other comorbidities besides diabetes (e.g., hypertension and sleep apnea) was comparable in both groups.
In 2011, de Gordejuela et al conducted a study to determine whether SG was as effective as gastric bypass on improving or resolving diabetes in patients with obesity. Ninety patients (60 RYGB and 30 SG) were included. in the study. Average BMI was 46kg/m2 and 57 kg/m2 for the gastric bypass and SG group, respectively. The fasting glycemia was 10.6mmol/L and 8.1mmol/L and the glycated hemoglobin was 8.1 and 7.3 percent in the RYGB and SG groups, respectively. No significant differences were seen in the amount of weight loss after two years between the two techniques. The resolution of diabetes was also the same (91.8 vs. 88.9%, nonsignificant [NS] Figure 1). The major criticisms from opponents of SG is that this effect is only seen in patients with morbid obesity and not in smaller patients, indicating that the weight loss alone is the mechanism of action in the procedure’s effectiveness rather than some sort of hormonal effect like the exclusion of the duodenum seen in gastric bypass.
Studies done in patients with low BMI (30 to 35kg/m2) have confirmed the efficacy of SG in the treatment of T2DM in patients without morbid obesity. Abbatini et al showed a T2DM cure rate of 88.8 percent without undesirable EWL in patients with BMIs between 30 and 35kg/m2 who underwent SG. It seems that it could be an independent weight phenomenon, as the glucose changes occur within the hospital stay or just a few days after SG.
In one study using obese rats, conducted by Chambers et al SG was found to be as effective as RYGB for increasing secretion of GLP-1 and insulin and improving hepatic sensitivity to insulin, effects that are independent of weight loss. Administration of a GLP-1 receptor antagonist prevented improvements in glucose and insulin responses after a meal among rats that received RYGB or LSG.
In a recent study of the surgical treatments of T2DM in patients with morbid obesity, authors used case-matched cohorts to compare RYGB and DS was found to be superior in reducing HbA1c and medication score (7.7±1.8 to 5.3±0.7 percent). Impressively, total resolution of T2DM occurred in 81.5 and 48.1 percent of DS and RYGB patients, respectively, one year postoperatively (P=0.02).24 This report emphasizes that DS is ultimately the best procedure for diabetes reversal in patients with morbid obesity, however, the procedure comes with a heavy mirconutritional price and some adverse events, which have been reported in patients who have undergone DS.
Given the vast data on SG and my operating experience, I believe that the best strategy for treatment of patients with obesity and T2DM would be to do an SG. If after the initial SG procedure, patients do not respond, the procedure can be revised to a DS. Another strategy is to perform SG on patients who have a failed gastric bypass, which is a difficult task to perform years after the initial operation. At my facility, however, I have demonstrated that this strategy is technically possible in selected patients.
With studies now demonstrating SG’s excellent effect beyond five years postoperatively, one can be confident that this surgery is likely to surpass both gastric bypass and adjustable gastric banding for patients with severe or morbid obesity and T2DM. This will be the first line of treatment as failures of SG, likely to be more than 15 percent, will be treated with an added intestinal component, such as duodeno-jejunal bypass, duodenal switch (duodeno-ileostomy), or ileal interposition. Currently, it is unknown which added component would be best, but I suspect a patient’s initial BMI, severity of T2DM, and genetic background would be important considerations.
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Category: Diabetes Perspective