P values are from modeled between-group changes from baseline to 2 years.
To convert total, low-density lipoprotein, and high-density lipoprotein cholesterol to millimoles per liter, multiply by 0.259; to convert triglycerides to millimoles per liter, multiply by 0.0113.
eTable 1. Nutritional Supplements Reported Taken 2 Years Postsurgery
eTable 2. Vitamins, Other Markers of Nutritional Status and Liver Enzymes
eTable 3. SF-36 Norm-Adjusted Dimensional Scores and Summary Scores
eFigure 1. Illustrations of Standard and Distal Gastric Bypass
eFigure 2a. Gastro-intestinal Symptoms Reported 2 Years after Surgery
eFigure 2b. Questions from the Bowel-function Questionnaire 2 Years after Surgery
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Risstad H, Svanevik M, Kristinsson JA, et al. Standard vs Distal Roux-en-Y Gastric Bypass in Patients With Body Mass Index 50 to 60: A Double-blind, Randomized Clinical Trial. JAMA Surg. 2016;151(12):1146–1155. doi:10.1001/jamasurg.2016.2798
What is the difference in body weight loss during 2 years after either standard or distal Roux-en-Y gastric bypass in patients with severe obesity?
In this double-blind, randomized clinical trial that included 113 patients with a body mass index of 50 to 60, the body mass index loss was 17.8 two years after standard gastric bypass and 17.2 two years after distal gastric bypass, a nonsignificant difference.
Distal gastric bypass was not associated with a greater body mass index reduction than standard gastric bypass 2 years after surgery.
Up to one-third of patients undergoing bariatric surgery have a body mass index (BMI) of more than 50. Following standard gastric bypass, many of these patients still have a BMI greater than 40 after peak weight loss.
To assess the efficacy and safety of standard gastric bypass vs distal gastric bypass in patients with a BMI of 50 to 60.
Design, Setting, and Participants
Double-blind, randomized clinical parallel-group trial at 2 tertiary care centers in Norway (Oslo University Hospital and Vestfold Hospital Trust) between May 2011 and April 2013. The study included 113 patients with a BMI of 50 to 60 aged 20 to 60 years. The 2-year follow-up was completed in May 2015.
Standard gastric bypass (alimentary limb, 150 cm) and distal gastric bypass (common channel, 150 cm), both with a biliopancreatic limb of 50 cm and a gastric pouch of about 25 mL.
Main Outcomes and Measures
Primary outcome was the change in BMI from baseline until 2 years after surgery. Secondary outcomes were cardiometabolic risk factors, nutritional outcomes, adverse events, gastrointestinal symptoms, and health-related quality of life.
At baseline, the mean age of the patients was 40 years (95% CI, 38-41 years), 65% were women, mean BMI was 53.5 (95% CI, 52.9-54.0), and mean weight was 158.8 kg (95% CI, 155.3-162.3 kg). The mean reduction in BMI was 17.8 (95% CI, 16.9-18.6) after standard gastric bypass and 17.2 (95% CI, 16.3-18.0) after distal gastric bypass, and the mean between-group difference was 0.6 (95% CI, −0.6 to 1.8; P = .32). Reductions in mean levels of total and low-density lipoprotein cholesterol were greater after distal gastric bypass than standard gastric bypass, and between-group differences were 19 mg/dL (95% CI, 11-27 mg/dL ) and 28 mg/dL (95% CI, 21 to 34 mg/dL), respectively (P < .001 for both). Reductions in fasting glucose levels and hemoglobin A1c were greater after distal gastric bypass. Secondary hyperparathyroidism and loose stools were more frequent after distal gastric bypass. The number of adverse events and changes in health-related quality of life did not differ between the groups. Importantly, 1 patient developed liver failure and 2 patients developed protein-caloric malnutrition treated by elongation of the common channel following distal gastric bypass.
Conclusions and Relevance
Distal gastric bypass was not associated with a greater BMI reduction than standard gastric bypass 2 years after surgery. However, we observed different changes in cardiometabolic risk factors and nutritional markers between the groups.
Clinicaltrials.gov Identifier: NCT00821197.
In the United States, up to one-third of patients undergoing bariatric surgery have a preoperative body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of more than 50.1 Laparoscopic Roux-en-Y gastric bypass is a commonly used bariatric procedure that leads to sustained weight loss and improves weight-related disease. The average percentage of body weight loss appears to be remarkably consistent across patient cohorts and range of BMIs.2-7 This may help explain the observation that among patients with very high BMI, many still experience morbid obesity after a gastric bypass procedure.8-10 We have previously shown that 5 years after standard gastric bypass, more than half of the patients with initial BMI of 50 to 60 had a BMI of more than 40.11
Different modifications of gastric bypass have been used to improve weight loss and outcome with regard to obesity-related diseases in patients with very high BMI. However, few randomized studies have been undertaken to compare the outcomes obtained with different lengths of the intestinal limbs involved (the alimentary limb, biliopancreatic limb, and common channel).12-14 Empirical findings with various gastric bypass limb lengths suggest that there exists a delicate balance between greater weight loss, with its associated health benefits, and the risk of surgical complications, diarrhea, and nutritional deficiencies.15-17 Distal gastric bypass refers to a variant of gastric bypass where the distance from the small bowel anastomosis (enteroenteroanastomosis) to the ileocecal valve is short, giving a short common channel. Distal gastric bypass could lead to greater weight loss and greater improvements of comorbid conditions compared with standard gastric bypass, but possibly at the cost of greater adverse nutritional effects. To our knowledge, this has not previously been tested in a randomized clinical study.
We therefore conducted a randomized clinical trial of standard and distal gastric bypass in patients with a BMI between 50 and 60. We aimed to test the hypothesis that BMI loss would be larger after distal gastric bypass than standard gastric bypass. We also compared the effects of the procedures with regards to cardiometabolic risk factors, nutritional outcomes, adverse events, health-related quality of life, and gastrointestinal adverse effects.
The methods applied in our double-blind, parallel-group randomized clinical trial of standard vs distal gastric bypass have previously been described in a report of perioperative outcome.18 Briefly, all referred patients aged 18 to 60 years with a BMI of 50 to 60 were assessed for inclusion at 2 tertiary care centers in Norway between May 2011 and April 2013. Patients with previous bariatric or major abdominal surgery, previously diagnosed urolithiasis, chronic liver disease, other severe somatic illness, or psychiatric diseases or substance abuse were excluded. The 2-year follow-up was completed in May 2015.
We used permuted-block randomization with random blocks of 4 and 6 generated by a person not involved in patient treatment. Eligible patients were randomly assigned to undergo either standard gastric bypass or distal gastric bypass in a 1:1 allocation ratio. Patients, follow-up study personnel at the outpatient clinic, clinicians providing outpatient follow-up care, and the statistician were unaware of treatment allocation.
The study was approved by the Regional Ethics Committees for Medical and Health Research. The formal trial protocols can be found in Supplement 1. All patients provided written and informed consent.
All patients followed a low-calorie diet (approximately 1000 kcal/d) 3 weeks prior to surgery. An antegastric antecolic Roux-en-Y configuration with a gastric pouch of about 25 mL and a biliopancreatic limb of 50 cm were constructed during both procedures. The standard gastric bypass included an alimentary limb of 150 cm, whereas the distal gastric bypass had a common channel of 150 cm (eFigure 1 in Supplement 2). Identical vitamin and mineral supplementation was prescribed to both groups: oral daily supplementation with 1-tablet multivitamins, 1000-mg calcium carbonate, 800-IU vitamin D3, and 65- to 200-mg iron. Intramuscular injections of 1 mg vitamin B12 were given every third month. Daily oral supplementation with 500 mg ursodeoxycholic acid was prescribed for 6 months postsurgery to reduce the risk of gallstone formation. Follow-up included a physical examination and blood tests at 6 weeks, 6 months, 1 year, and 2 years after surgery.
Body weight, fat mass, and fat-free mass were measured to the nearest 0.1 kg using a calibrated digital scale (Tanita-BC 418 MA; Tanita Corporation) with the patient wearing light clothing and no shoes. Height was measured with a fixed stadiometer.
Venous blood samples were obtained after an overnight fast. Comorbidities were assessed, and medications and supplements were adjusted according to predefined treatment algorithms. Blood pressure was measured 3 times in the sitting position after a few minutes of rest, and the last 2 measurements were averaged. Hypertension was defined as either systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, or the use of antihypertensive medication.19 Type 2 diabetes was defined as hemoglobin A1c (HbA1c) level of at least 6.5% (to convert to proportion of total hemoglobin, multiply by 0.01) or the use of glucose-lowering medication.20 Complete remission of type 2 diabetes was defined as HbA1c level of 6.0% or lower and fasting glucose level less than 101 mg/dL (to convert to millimoles per liter, multiply by 0.0555), and partial remission was defined as as HbA1c level less than 6.5% and fasting glucose level of 101 to 124 mg/dL, both assuming no use of glucose-lowering drugs for at least a year.21 Metabolic syndrome was defined according to established criteria.22 The presence of sleep apnea was based on previously confirmed diagnosis. Secondary hyperparathyroidism was defined as parathyroid hormone greater than upper reference limit (>66 pg/mL; to convert to nanograms per liter, mulitply by 1) in the absence of hypercalcemia. Iron deficiency was defined as ferritin levels less than 15 ng/mL (to convert to picomoles per liter, multiply by 2.247).
All adverse events requiring intervention from 30 days postoperatively until 2 years were included regardless of whether they were judged related to the initial procedure or not. Information regarding adverse events (medical visits, examinations, operations, or hospital admissions) was retrieved from all patients at each study visit. Earlier complications have previously been reported and are excluded here because differing surgical experiences of the 2 procedures might bias the findings.18 The classification of adverse events was performed without prior knowledge of the assigned treatment.
The patients completed the Gastrointestinal Symptoms Rating Scale and a bowel function questionnaire to assess gastrointestinal symptoms and bowel habits at 2 years.23,24
Generic health-related quality of life was assessed using validated Norwegian versions of the Short Form–36 Health Survey and scored with certified software (QualityMetric Health Outcomes Scoring Software 4.0/4.5).25
The sample size estimates have been described elsewhere.18 We calculated that 88 patients would give a power of more than 80% to detect a BMI difference between groups of 3.0 at follow-up (α = .05). To allow for possible dropouts, we included 113 patients in total.
We fitted linear mixed models to all continuous outcomes with repeated measurements. Each model contained fixed effects for treatment, time (measured in weeks after surgery), treatment × time interaction, and a random intercept. The time development was modeled as piecewise linear with a knot at 1 year after surgery, such that the models allowed for 1 development from baseline to 1 year after surgery and another development from 1 year to 2 years after surgery. Based on the linear mixed models, we estimated mean treatment group values with 95% CIs for 2 time points: baseline and 2 years after surgery. We also estimated the mean group changes from baseline to 2 years and the between-group difference in change from baseline to 2 years. The Fisher mid-P test (2 categories) or the Fisher-Freeman-Halton test (more than 2 categories) was used to compare independent proportions. Patient-reported gastrointestinal symptoms were analyzed with the Mann-Whitney U test or independent-samples t test. A 2-sided 5% level of significance was used for all analyses. We used Stata 13.1 (StataCorp LP) and IBM SPSS Statistics for Windows, version 22.0, to perform the statistical analyses (IBM Corporation).
One hundred thirteen patients received treatment as randomized; 57 receiving a standard gastric bypass and 56 receiving a distal gastric bypass (Figure 1). Baseline characteristics are presented in Table 1. At baseline, there was a random imbalance between patients with type 2 diabetes (13 vs 18 patients in the standard and distal gastric bypass group, respectively). The 2-year follow-up rate was 97% (110 of 113 patients).
The mean reduction in BMI was 17.8 (95% CI, 16.9-18.6) after standard gastric bypass and 17.2 (95% CI, 16.3-18.0) after distal gastric bypass, and the mean between-group difference was 0.6 (95% CI, −0.6 to 1.8; P = .32) (Table 2, Figure 2). Mean total weight loss was 35.1% (95% CI, 32.1%-38.1%) after standard gastric bypass and 34.0% (95% CI, 32.1%-35.9%) after distal gastric bypass (P = .54). Similarly, excess BMI lost was 66.1% (60.5%-71.7%) and 63.6% (60.0%-67.3%) (P = .46).
Total and low-density lipoprotein cholesterol decreased more after distal gastric bypass compared with standard gastric bypass (Figure 2, Table 2), while high-density lipoprotein cholesterol increased more after standard gastric bypass. The reductions in fasting triglycerides did not differ between the groups. The reductions in fasting serum glucose and in HbA1c were greater after distal than standard gastric bypass (Table 2, Figure 2). Of patients with type 2 diabetes at baseline, 9 of 11 with standard gastric bypass (82%) and 12 of 16 with distal gastric bypass (75%) achieved complete remission, 1 (9%) vs 3 (19%) had partial remission, and 1 patient in both groups still had type 2 diabetes at follow-up (P = .81 between groups). At 2 years, 1 patient with standard gastric bypass was taking metformin, whereas all other patients had stopped using glucose-lowering medication. No patients developed new-onset type 2 diabetes.
There were no differences in changes in systolic and diastolic blood pressure across the groups (Table 2). Of patients with hypertension at baseline, 26 of 34 with standard gastric bypass (77%) and 14 of 34 with distal gastric bypass (41%) did not have hypertension at 2 years (P = .004 between groups). Furthermore, 16 of 20 patients (80%) and 17 of 25 patients (68%) had stopped using antihypertensive medication after standard and distal gastric bypass, respectively (P = .41). Ten of 16 patients (63%) and 10 of 13 patients (77%) using continuous positive airway pressure for obstructive sleep apnea at baseline had stopped the treatment 2 years after standard and distal gastric bypass, respectively (P = .34). At 2 years, 38 of 44 patients (86%) and 34 of 47 patients (72%) no longer fulfilled the criteria for the metabolic syndrome after standard and distal gastric bypass, respectively (P = .10 between groups). No patients developed new-onset metabolic syndrome.
There was no difference in the reported use of vitamin and mineral supplements between the groups at 2 years (eTable 1 in Supplement 2). Changes in mean concentrations of some of the vitamins were different in the 2 groups, but for all measured vitamins, the mean concentrations were either stable or increased from baseline to 2 years (eTable 2 in Supplement 2). We observed a larger increase in the mean concentration of parathyroid hormone after distal gastric bypass as opposed to standard gastric bypass (eTable 2 in Supplement 2). At 2 years, 19 of 54 patients (35%) had secondary hyperparathyroidism after standard gastric bypass compared with 32 of 53 patients (60%) after distal gastric bypass (P = .01). The mean concentrations of hemoglobin and ferritin were reduced without between-group differences. Two patients who had distal gastric bypass developed severe iron deficiency that was treated by either blood transfusions or iron injections (Table 3). At 2 years, 11 of 54 patients (20%) with standard gastric bypass and 8 of 52 patients (15%) with distal gastric bypass had iron deficiency (P = .53). Two of 54 patients (4%) in the standard gastric bypass group and 5 of 52 patients (10%) in the distal gastric bypass group had albumin levels below reference values (P = .19). One patient in the standard gastric bypass group and 3 patients in the distal gastric bypass group developed protein-caloric malnutrition (Table 3). Two of the patients with distal gastric bypass had the elongation of the common channel reoperated on after 22 and 24 months, both with improved nutritional status. The third patient had liver cirrhosis not diagnosed prior to surgery and developed severe protein-caloric malnutrition and liver failure that did not improve after nutritional support and later died of liver failure 11 months after surgery. Overall, we found no statistically significant differences between the groups with regard to adverse events, but patients with standard gastric bypass had more hospital admissions than patients with distal gastric bypass (Table 3).
At 2 years, there were no between-group differences in the Gastrointestinal Symptoms Rating Scale symptom dimensions including diarrhea, indigestion, constipation, abdominal pain, or gastroesophageal reflux (eFigure 2A in Supplement 2). However, patients reported more frequent and loose stools and greater social limitations owing to bowel function after distal gastric bypass (eFigure 2B in Supplement 2). In general, health-related quality of life improved in both groups after surgery, with the highest increases in physical functioning and general health and with no between-group differences (eTable 3 in Supplement 2). The physical summary score was improved and the mental summary score was unchanged for both surgical groups, with no between-group differences.
In contrast with our hypothesis, we observed no difference in weight reduction between standard and distal Roux-en-Y gastric bypass at 2 years. The study demonstrates that creating a distal gastric bypass with a common channel of 150 cm was not associated with greater weight loss or other anthropometric measures up to 2 years when the biliopancreatic limb was kept at 50 cm. This contrasts with the findings of most of the existing literature that addresses the importance of intestinal limb lengths on weight loss.12,13 However, one small nonrandomized study found similar weight loss after comparing standard and distal gastric bypass with the same limb lengths as applied in our study.26 Our findings also contrast reports of distal gastric bypass performed as a secondary procedure owing to insufficient weight loss after standard gastric bypass. However, in many series, other limb lengths than explored in the present study were applied.27-29
Studies suggest a critical limit of the common channel length at around 100 cm or less for developing severe nutritional adverse effects, although the threshold varies between individuals.15,27 We used a common channel of 150 cm in an attempt to improve weight loss while lowering the risk of nutritional adverse effects. Although our observation of similar weight loss (51 kg) in the 2 surgical groups may indicate comparable macronutrient absorption, we observed more signs of malabsorption after distal gastric bypass including lower albumin levels, a higher prevalence of secondary hyperparathyroidism, and more patient-reported loose stools. Accordingly, we cannot exclude the possibility that patients who underwent distal gastric bypass surgery had a compensatory larger calorie intake or lower energy expenditure than patients who underwent standard gastric bypass. A distal gastric bypass variant with a longer biliopancreatic limb and a shorter alimentary limb30 or a variant with shorter common channel may also induce greater weight loss but at the cost of greater nutritional adverse effects.15,16,27,31
We selected patients with a BMI between 50 and 60 because for patients with lower BMIs, weight loss is often considered sufficient after standard gastric bypass, and for patients with higher BMIs, other procedures may be considered necessary. In a previous randomized study of standard gastric bypass or duodenal switch in patients with a BMI of 50 to 60, we have reported significantly more weight loss after duodenal switch but at the expense of more adverse effects.11,32-34 Because most bariatric surgeons have experience with gastric bypass, surgeons may consider distal gastric bypass a less technically challenging procedure than duodenal switch. Our variant of distal gastric bypass included a short biliopancreatic limb, which means that most of the small bowel still was kept in the digestive stream. In duodenal switch, the biliopancreatic limb is longer and the common channel shorter than in our variant of distal gastric bypass. Both these factors could contribute to explain the superior weight loss of duodenal switch over distal gastric bypass.
Except for more patients with hospital admissions after standard gastric bypass, we found no differences with regard to long-term adverse events or in changes in health-related quality of life between the groups. However, the risk of nutritional detrimental effects in our variant of distal gastric bypass should not be ignored. Two patients developed severe diarrhea and protein-caloric malnutrition after distal gastric bypass and required reoperation with prolongation of the common channel, and 1 patient with liver cirrhosis died of liver failure. These findings could illustrate an individual threshold for developing adverse effects and the need for close monitoring of patients. As described in our report on perioperative outcomes, all early reoperations were in the distal gastric bypass group, which may indicate different technical challenges or surgeon-related experience with the techniques.18
Serum total cholesterol and low-density lipoprotein cholesterol levels declined more after distal than standard gastric bypass. The between-group differences are comparable with the beneficial effect of high vs low doses of lipid-lowering therapy with statins and could potentially affect cardiovascular risk.35,36 A similar pattern has been demonstrated in studies of standard gastric bypass in comparison with more malabsorptive procedures.33,37,38 This difference could relate to larger weight loss and/or reduced cholesterol and bile acid reabsorption in the small intestine.39 The greater increase in high-density lipoprotein cholesterol after standard gastric bypass is consistent with a 2015 review that observed greater increase in high-density lipoprotein cholesterol after gastric bypass than after more malabsorptive procedures.40 Despite similar changes in mean levels of blood pressure, we found a greater remission rate of hypertension after standard gastric bypass. The finding of larger reductions of fasting glucose and HbA1c should be interpreted with caution because it may be owing to a random unbalanced distribution of patients with type 2 diabetes at baseline.
Overall, our findings indicate that distal gastric bypass may have greater beneficial effects on some cardiometabolic risk factors than standard gastric bypass. However, the distal gastric bypass group had a greater increase in parathyroid hormone and a higher prevalence of secondary hyperparathyroidism as well as a lower increase in high-density lipoprotein cholesterol and lower remission of hypertension, with a possibly negative effect on bone health41 and cardiovascular disease.42,43
The strengths of this study include the randomized, double-blind design, standardized surgical procedures, nearly complete follow-up at all study visits, and the comprehensive evaluation. Our patients were recruited from public hospitals, and treatment was independent of insurance or personal finance and health insurance status, which may limit some forms of patient selection bias. Our findings may not extrapolate to cohorts where distal gastric bypass is performed as a secondary procedure owing to insufficient weight loss. The study was not powered to assess differences in secondary outcomes. We did not quantify malabsorption of calories, record dietary intakes, or investigate other mechanisms potentially contributing to weight loss.
Two ongoing randomized trials are investigating the outcome of other variants of distal gastric bypass. One of these studies uses a 100-cm common channel,44 and the other combines a 150-cm common channel with a 200-cm biliopancreatic limb.45 When long-term findings from these randomized trials are reported, well-conducted systematic literature reviews will hopefully provide patients, clinicians, and policy makers with further robust and relevant information regarding the role of distal gastric bypass in the surgical treatment of severe obesity.
Weight loss was not larger after distal compared with standard gastric bypass 2 years after surgery. Changes in several cardiometabolic risk factors and nutritional markers were different in the 2 groups.
Corresponding Author: Hilde Risstad, MD, Oslo University Hospital, PO Box 4959, N-0424 Oslo, Norway (email@example.com).
Accepted for Publication: June 1, 2016.
Published Online: September 14, 2016. doi:10.1001/jamasurg.2016.2798
Author Contributions: Drs Risstad and Svanevik are both first authors of this work, had full access to all of the data, and take responsibility for the integrity of the data and the accuracy of the data analyses.
Concept and design: Kristinsson, Hjelmesæth, Aasheim, Sovik, Sandbu, Mala.
Acquisition, analysis, or interpretation of data: All Authors.
Drafting of the manuscript: Risstad, Svanevik, Mala.
Critical revision of the manuscript for important intellectual content: All Authors.
Statistical analysis: Risstad, Karlsen, Fagerland.
Obtaining funding: Hjelmesæth, Sandbu, Mala.
Administrative, technical, or material support: Risstad, Svanevik, Hjelmesæth, Sovik, Karlsen, Sandbu, Mala.
Study supervision: Kristinsson, Hjelmesæth, Sandbu, Mala.
Conflict of Interest Disclosures: Drs Kristinsson and Mala report receiving travel reimbursements from Johnson and Johnson and Covidien. No other disclosures are reported.
Funding/Support: Drs Risstad and Svanevik’s research fellowships were funded by the Southern and Eastern Norway Health Authority.
Role of the Funder/Sponsor: The Southern and Eastern Norway Health Authority had no role in the design and conduct of the study; data collection, management, analyses, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: We thank Gunn Signe Jakobsen, MD (Vestfold Hospital Trust), for her contribution to study planning and protocol development; Carl Fredrik Schou, MD (Oslo University Hospital), for his contribution to study planning and surgical expertise; Linda Mathisen (Vestfold Hospital Trust) and Marianne Sæther (Oslo University Hospital), for general project support; Johanna Molin, MD (Vestfold Hospital Trust), for clinical management of patients; Matthew McGee, Vestfold Hospital Trust, for proofreading the manuscript; and the Hormone Laboratory and Department of Nutrition, Oslo University Hospital, for contribution with blood sample analyses for both study centers. None of the contributors received compensation for their roles in the study. Finally, we thank all the patients for participating in the study.
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