Long-Term Outcomes of Medical Management vs Bariatric Surgery in Type 2 Diabetes.

Importance: Randomized clinical trials of bariatric surgery have been limited in size, type of surgical procedure, and follow-up duration. Objective: To determine long-term glycemic control and safety of bariatric surgery compared with medical/lifestyle management of type 2 diabetes. Design, Setting, and Participants: ARMMS-T2D (Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes) is a pooled analysis from 4 US single-center randomized trials conducted between May 2007 and August 2013, with observational follow-up through July 2022. Intervention: Participants were originally randomized to undergo either medical/lifestyle management or 1 of the following 3 bariatric surgical procedures: Roux-en-Y gastric bypass, sleeve gastrectomy, or adjustable gastric banding. Main Outcome and Measures: The primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 7 years for all participants. Data are reported for up to 12 years. Results: A total of 262 of 305 eligible participants (86%) enrolled in long-term follow-up for this pooled analysis. The mean (SD) age of participants was 49.9 (8.3) years, mean (SD) body mass index was 36.4 (3.5), 68.3% were women, 31% were Black, and 67.2% were White. During follow-up, 25% of participants randomized to undergo medical/lifestyle management underwent bariatric surgery. The median follow-up was 11 years. At 7 years, HbA1c decreased by 0.2% (95% CI, -0.5% to 0.2%), from a baseline of 8.2%, in the medical/lifestyle group and by 1.6% (95% CI, -1.8% to -1.3%), from a baseline of 8.7%, in the bariatric surgery group. The between-group difference was -1.4% (95% CI, -1.8% to -1.0%; P < .001) at 7 years and -1.1% (95% CI, -1.7% to -0.5%; P = .002) at 12 years. Fewer antidiabetes medications were used in the bariatric surgery group. Diabetes remission was greater after bariatric surgery (6.2% in the medical/lifestyle group vs 18.2% in the bariatric surgery group; P = .02) at 7 years and at 12 years (0.0% in the medical/lifestyle group vs 12.7% in the bariatric surgery group; P < .001). There were 4 deaths (2.2%), 2 in each group, and no differences in major cardiovascular adverse events. Anemia, fractures, and gastrointestinal adverse events were more common after bariatric surgery. Conclusion and Relevance: After 7 to 12 years of follow-up, individuals originally randomized to undergo bariatric surgery compared with medical/lifestyle intervention had superior glycemic control with less diabetes medication use and higher rates of diabetes remission. Trial Registration: ClinicalTrials.gov Identifier: NCT02328599.

Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D): Study rationale, design, and methods.

AIMS: Long-term data from randomized clinical trials comparing metabolic (bariatric) surgery versus a medical/lifestyle intervention for treatment of patients with obesity/overweight and type 2 diabetes (T2D) are lacking. The Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) is a consortium of four randomized trials designed to compare long-term efficacy and safety of surgery versus medical/lifestyle therapy on diabetes control and clinical outcomes. MATERIALS AND METHODS: Patients with T2D and body mass index (BMI) of 27-45 kg/m2 who were previously randomized to metabolic surgery (Roux-en-Y gastric bypass, adjustable gastric band, or sleeve gastrectomy) versus medical/lifestyle intervention in the STAMPEDE, SLIMM-T2D, TRIABETES, or CROSSROADS trials have been enrolled in ARMMS-T2D for observational follow-up. The primary outcome is change in glycated haemoglobin after a minimum 7 years of follow-up, with additional analyses to determine rates of diabetes remission and relapse, as well as cardiovascular and renal endpoints. RESULTS: In total, 302 patients (192 surgical, 110 medical/lifestyle) previously randomized in the four parent studies were eligible for participation in the ARMMS-T2D observational study. Participant demographics were 71% white, 27% African-American and 68% female. At baseline: age, 50 ± 8 years; BMI, 36.5 ± 3.5 kg/m2 ; duration of diabetes, 8.8 ± 5.6 years; glycated haemoglobin, 8.6% ± 1.6%; and fasting glucose, 168 ± 64 mg/dl. More than 35% of patients had a BMI <35 kg/m2 . CONCLUSIONS: ARMMS-T2D will provide the largest body of long-term, level 1 evidence to inform clinical decision-making regarding the comparative durability, efficacy and safety of metabolic surgery relative to a medical/lifestyle intervention among patients with T2D, including those with milder class I obesity or mere overweight.

Gut adaptation after gastric bypass in humans reveals metabolically significant shift in fuel metabolism.

OBJECTIVE: Roux-en-Y gastric bypass surgery (RYGB) is among the most effective therapies for obesity and type 2 diabetes, and intestinal adaptation is a proposed mechanism for these effects. It was hypothesized that intestinal adaptation precedes and relates to metabolic improvement in humans after RYGB. METHODS: This was a prospective, longitudinal, first-in-human study of gene expression (GE) in the "Roux limb" (RL) collected surgically/endoscopically from 19 patients with and without diabetes. GE was determined by microarray across six postoperative months, including at an early postoperative (1 month ± 15 days) time point. RESULTS: RL GE demonstrated tissue remodeling and metabolic reprogramming, including increased glucose and amino acid use. RL GE signatures were established early, before maximal clinical response, and persisted. Distinct GE fingerprints predicted concurrent and future improvements in HbA1c and in weight. Human RL exhibited GE changes characterized by anabolic growth and shift in metabolic substrate use. Paradoxically, anabolic growth in RL appeared to contribute to the catabolic state elicited by RYGB. CONCLUSIONS: These data support a role for a direct effect of intestinal energy metabolism to contribute to the beneficial clinical effects of RYGB, suggesting that related pathways might be potential targets of therapeutic interest for patients with obesity with or without type 2 diabetes.

Five-year attrition, active enrollment, and predictors of level of participation in the Longitudinal Assessment of Bariatric Surgery (LABS-2) study.

BACKGROUND: Reporting high-quality bariatric surgery outcomes depends on participant attrition and level of study participation among enrolled participants. OBJECTIVES: Our aims are to report participant attrition, active enrollment, and level of participation, and to evaluate pre-surgery sociodemographic, physical health, and psychosocial factors as predictors of attrition and level of participation through 5 years. SETTING: The Longitudinal Assessment of Bariatric Surgery-2 study which enrolled 2458 adults undergoing a first bariatric surgical procedure at 1 of 6 US cites from 2006 through 2009. METHODS: In-person research assessments were conducted pre-surgery and annually for five years. Extensive retention strategies including offering remote assessments (telephone, email, mail, or a combination) were fully implemented in 2009. Among living participants, including those inactivated, annual follow-up assessments were categorized as in-person, remote or missed through 5 years. RESULTS: By year 5, 1.7% of participants had died and 3.2% had withdrawn or were inactivated by the study staff; thus, attrition was 4.9% (n = 121). Controlling for site and calendar year, missed assessments increased from 14.7%-21.8% between years 1 and 2 and then stayed relatively stable (20.8%-19.6%) for years 3-5. Younger age, male sex, White race, lower body mass index, smoking, illicit drug use, and higher weight loss expectations preoperatively were independently associated with a higher likelihood of a missed versus in-person assessment across follow-up. CONCLUSION: The LABS-2 participant attrition was low. The percentage of missed assessments did not increase after year 2, perhaps due to implementation of a comprehensive retention plan. Predictors of missed assessments highlight subgroups to target for focused retention efforts.

American Society of Metabolic and Bariatric Surgery consensus statement on laparoscopic adjustable gastric band management.

BACKGROUND: Laparoscopic adjustable gastric band (LAGB) management continues to be an important part of many metabolic and bariatric surgery practices. OBJECTIVES: To replace the existing American Society for Metabolic and Bariatric Surgery (ASMBS) LAGB adjustment credentialing guidelines for physician extenders with consensus statements that reflect the current state of LAGB management. SETTING: ASMBS Integrated Health Clinical Issues Committee. METHODS: A modified Delphi process using a 2-stage consensus approach was conducted on LAGB management. Thirty-four consensus statements were developed following a literature search on a wide range of LAGB topics. A 5-point Likert scale was implemented to measure consensus agreement with a Delphi panel of 39 expert participants who were invited and agreed to participate in 2 rounds of Delphi questionnaires. Consensus was set a priori at 75% agreement, defined as the proportion of participants responding with agreement (i.e., 4 or 5) or disagreement (i.e., 1 or 2) on the Likert scale. RESULTS: Consensus was reached on 74% (25 of 34) of the LAGB management statements. In Delphi round 1, 95% (37 of 39) of the participants responded to 34 consensus statements; 21 of the statements (62%) met the 75% criteria for consensus. Thirty-one participants (80%) responded in round 2, shifting the agreement on 4 more statements to the 75% threshold. CONCLUSION: The ASMBS consensus statement on LAGB management is intended to guide practice with current evidence-based knowledge and professional experience. The ASMBS is not a credentialing body and does not seek to guide credentialing with this document.

Diabetes Remission in the Alliance of Randomized Trials of Medicine Versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D).

OBJECTIVE: The overall aim of the Alliance of Randomized Trials of Medicine versus Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) consortium is to assess the durability and longer-term effectiveness of metabolic surgery compared with medical/lifestyle management in patients with type 2 diabetes (NCT02328599). RESEARCH DESIGN AND METHODS: A total of 316 patients with type 2 diabetes previously randomly assigned to surgery (N = 195) or medical/lifestyle therapy (N = 121) in the STAMPEDE, TRIABETES, SLIMM-T2D, and CROSSROADS trials were enrolled into this prospective observational cohort. The primary outcome was the rate of diabetes remission (hemoglobin A1c [HbA1c] ≤6.5% for 3 months without usual glucose-lowering therapy) at 3 years. Secondary outcomes included glycemic control, body weight, biomarkers, and comorbidity reduction. RESULTS: Three-year data were available for 256 patients with mean 50 ± 8.3 years of age, BMI 36.5 ± 3.6 kg/m2, and duration of diabetes 8.8 ± 5.7 years. Diabetes remission was achieved in more participants following surgery than medical/lifestyle intervention (60 of 160 [37.5%] vs. 2 of 76 [2.6%], respectively; P < 0.001). Reductions in HbA1c (Δ = -1.9 ± 2.0 vs. -0.1 ± 2.0%; P < 0.001), fasting plasma glucose (Δ = -52 [-105, -5] vs. -12 [-48, 26] mg/dL; P < 0.001), and BMI (Δ = -8.0 ± 3.6 vs. -1.8 ± 2.9 kg/m2; P < 0.001) were also greater after surgery. The percentages of patients using medications to control diabetes, hypertension, and dyslipidemia were all lower after surgery (P < 0.001). CONCLUSIONS: Three-year follow-up of the largest cohort of randomized patients followed to date demonstrates that metabolic/bariatric surgery is more effective and durable than medical/lifestyle intervention in remission of type 2 diabetes, including among individuals with class I obesity, for whom surgery is not widely used.

Auricular nerve stimulation using the NSS-2 BRIDGE device to reduce opioid requirement following laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Evidence supports the use of complementary techniques to reduce pain and opioid use after surgery. The NSS-2 BRIDGE device (NBD; Innovative Health Solutions, Inc., Versailles, Indiana) modulates pain via stimulation of the nucleus of the auricular branch of the cranial nerves at the level of the brainstem and the limbic system. OBJECTIVE: To investigate the role of auricular nerve field stimulation for pain control following gastric bypass surgery. SETTINGS: U.S. academic medical center. METHODS: A total of 18 subjects were included. Subjects were divided in 2 groups: NBD group (n = 8) and a control group (n = 10). The NBD was placed following laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery in the recovery room. The effectiveness of NBD was assessed comparing the relative use of opioid consumption (oral morphine equivalents) and pain (0 = no pain to 10= worst possible pain) at 24 and 48 hours after surgery. In addition, the device tolerability (1-10) was assessed, with 8-10 considered excellent. Data were analyzed using unpaired t tests and presented as mean ± standard deviation. Alpha was set up at .1. RESULTS: Compared with the control group, the use of NBD was associated with a 60.2% reduction in oral morphine equivalents (38.15 vs 15.2 mg; P < .1) and a 28% reduction in pain (5.0 vs 3.6; P = .1) at 24 hours after surgery. The tolerability of NBD was reported to be excellent. CONCLUSIONS: This report suggests that NBD may represent an interesting alternative to control perioperative pain and limit opioid use following bariatric surgery. This needs to be confirmed by a placebo-controlled, randomized study.

Surgical placement of customized abdominal vagus nerve stimulating and gastrointestinal serosal surface recording electrodes.

Bioelectronic medical approaches to control vagus nerve-to-organ signaling have the potential to treat cardiac, respiratory, gastrointestinal (GI) and metabolic diseases, such as obesity. Unlike cervical vagus nerve stimulation (VNS), abdominal VNS could provide specific therapeutic control of the GI tract without off-target effects on thoracic organs; however, surgical approaches for abdominal VNS electrode placement are not well established. Moreover, optimal device configurations and additional placement of GI recording electrodes for closed-loop control are largely unknown. We designed VNS cuff and GI planar serosal electrodes and tested placement of these devices in laparoscopic surgery in two cadavers. We determined that electrode positioning on the ventral abdominal vagus nerve and gastric antrum was feasible but other sites, such as the duodenum and proximal stomach, were more difficult. The current investigation can guide potential placement and design of VNS cuff and GI electrodes for development of closed-loop GI therapeutic devices.

The Feasibility of Examining the Effects of Gastric Bypass Surgery on Intestinal Metabolism: Prospective, Longitudinal Mechanistic Clinical Trial.

BACKGROUND: Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the best treatment for severe obesity and its complications including type 2 diabetes mellitus (T2DM). Understanding the mechanisms responsible for the beneficial metabolic effects will help to engineer ways to improve the procedure or produce these effects without surgery. OBJECTIVE: The aim is to present data on recruitment and feasibility of a translational study designed to collect intestinal samples before and after bariatric surgery. The goal of biobanking is to allow future studies to test the hypothesis that the mechanism of action of RYGB involves specific changes in the postsurgical short- and long-term metabolism and morphology of the jejunum (Roux limb). Specifically, to test whether the intestine enhances its metabolism and activity after RYGB and increases its fuel utilization, we designed a prospective, longitudinal study, which involved the recruitment of candidates for RYGB with and without T2DM. We describe the tissue bank that we have generated, and our experience, hoping to further facilitate the performance of longitudinal mechanistic studies in human patients undergoing bariatric surgery and especially those involving post-RYGB intestinal biology. METHODS: We conducted a trial to characterize the effects of RYGB on intestinal metabolism. Intestinal tissue samples were collected from the jejunum at surgery, 1, 6, and 12 months postoperatively for the analysis of intestinal gene expression and metabolomic and morphologic changes. The target number of patients who completed at least the 6-month follow-up was 26, and we included a 20% attrition rate, increasing the total number to 32. RESULTS: To enroll 26 patients, we had to approach 79 potential participants. A total of 37 agreed to participate and started the study; 33, 30, and 26 active participants completed their 1-month, 6-month, and 12-month studies, respectively. Three participants withdrew, and 30 participants are still active. Altruism and interest in research were the most common reasons for participation. Important factors for feasibility and successful retention included (1) large volume case flow, (2) inclusion and exclusion criteria broad enough to capture a large segment of the patient population but narrow enough to ensure the completion of study aims and protection of safety concerns, (3) accurate assessment of willingness and motivation to participate in a study, (4) seamless integration of the recruitment process into normal clinical flow, (5) financial reimbursement and nonfinancial rewards and gestures of appreciation, and (6) nonburdensome follow-up visits and measures and reasonable time allotted. CONCLUSIONS: Human translational studies of the intestinal mechanisms of metabolic and weight changes after bariatric surgery are important and feasible. A tissue bank with unique samples has been established that could be used by investigators in many research fields, further enabling mechanistic studies on the effects of bariatric surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT02710370; https://clinicaltrials.gov/ct2/show/NCT02710370 (Archived by WebCite at http://www.webcitation.org/75HrQT8Dl).

Time-Dependent Molecular Responses Differ between Gastric Bypass and Dieting but Are Conserved Across Species.

The effectiveness of Roux-en-Y gastric bypass (RYGB) against obesity and its comorbidities has generated excitement about developing new, less invasive treatments that use the same molecular mechanisms. Although controversial, RYGB-induced improvement of metabolic function may not depend entirely upon weight loss. To elucidate the differences between RYGB and dieting, we studied several individual organ molecular responses and generated an integrative, interorgan view of organismal physiology. We also compared murine and human molecular signatures. We show that, although dieting and RYGB can bring about the same degree of weight loss, post-RYGB physiology is very different. RYGB induces distinct, organ-specific adaptations in a temporal pattern that is characterized by energetically demanding processes, which may be coordinated by HIF1a activation and the systemic repression of growth hormone receptor signaling. Many of these responses are conserved in rodents and humans and may contribute to the remarkable ability of surgery to induce and sustain metabolic improvement.

Retention and attrition in bariatric surgery research: an integrative review of the literature.

BACKGROUND: Bariatric surgery research, often longitudinal, bears the challenge of maintaining retention and decreasing attrition of participants to avoid bias. OBJECTIVES: To explore factors influencing the retention and attrition for bariatric surgical research participants. METHODS: Databases searched included: PubMed, CINAHL, Scopus, and others. As a secondary aim, studies reporting on retention/attrition factors in clinical follow-up visits were included. RESULTS: Of the 1145 articles retrieved, 44 met inclusion criteria, and underwent qualitative analysis. Four descriptive articles focused on longitudinal research participation and 40 on clinical follow-up visits. Willingness to participate in research was high (92%) and decreased with more invasive procedures or extra visits. A large observational longitudinal study presented 24-month retention/attrition data (92% for some data and 66% visit completion) and the retention strategies employed. One study indicated that research follow-up possibly increased clinical follow-up and another demonstrated a higher retention by increasing compensation. No consistent, modifiable demographic or psychosocial variables associated or predictive of retention or attrition in clinical follow-up were identified. CONCLUSIONS: Research on factors related to participant retention and attrition is sparse. It is essential for studies to document retention/attrition data. Existing research has demonstrated a patient willingness to participate in research and that retention strategies have been successful in the short term. Further research should explore the motivations, perspectives and attitudes of bariatric surgical research participants regarding participation and explore predictors to develop evidence-based retention strategies. Research has yet to identify consistent and modifiable demographic or psychosocial variables predictive of clinical follow-up, possibly due to the heterogeneity of follow-up across studies. Further investigation into follow-up definition, content, counseling approaches, and new telemedicine technologies may prove helpful in developing predictors and evidence-based strategies. The relationship between research and clinical retention and attrition deserves further characterization.

Elective cholecystectomy during laparoscopic Roux-en-Y gastric bypass: is it worth the wait?

BACKGROUND: Combined gastric bypass and cholecystectomy have been advocated for open bariatric procedures. Our goal was to evaluate the safety of this technique in laparoscopic bariatric surgery patients with gallstones diagnosed preoperatively. METHODS: 94 out of 556 consecutive morbidly obese patients (16.9%) underwent laparoscopic gastric bypass with simultaneous cholecystectomy (LGBP/LC) for cholelithiasis. RESULTS: 328 patients (59%) had a concomitant secondary procedure, most commonly cholecystectomy (28.7%). Preoperative BMI was 48.6 +/- 6.9 kg/m2 for LGBP/LC patients and 48.8 +/- 7.3 kg/m2 (P = 0.85) for LGBP alone. 5 patients had preoperative biliary colic; the others were asymptomatic for cholelithiasis. Postoperatively, at a mean follow-up of 7.6 +/- 6.7 months, the percent excess weight loss (%EWL) was 46.1 +/- 0.25 for the combined procedure vs 50.2 +/- 63.0 (P = 0.55) for LGBP alone. There were no conversions to open procedures for the LC. Port placement for the LGBP was not altered for LC. None required intraoperative cholangiography. Operative time for the combined procedure was 293.4 +/- 79.8 minutes vs 244.8 +/- 77.2 minutes for LGBP alone (P < 0.0001). Length of stay for the combined procedure was 4.35 +/- 10.8 days vs 2.69 +/- 1.8 days for LGBP alone (P = 0.0069). There were no postoperative bile leaks or bile duct injuries. CONCLUSION: Concomitant LGBP/LC is safe and feasible without altering port placement. Combining these procedures significantly increases operative time and nearly doubles the hospital stay.

Longitudinal Assessment of Bariatric Surgery (LABS): retention strategy and results at 24 months.

BACKGROUND: Retaining participants in observational longitudinal studies after bariatric surgery is difficult yet critical because the retention rate affects interpretation and generalizability of results. Strategies for keeping participants involved in such studies are not commonly published. The objective of this study was to review LABS retention strategies and present the 24-month retention data. METHODS: The LABS Consortium monitors an observational cohort study of 2458 adults enrolled before bariatric surgery at 10 centers within the United States (LABS-2). To maximize data completeness, the investigators developed retention strategies, including flexible scheduling, a call protocol, reminder letters, abbreviated visit options, honoraria, travel reimbursement, providing research progress reports, laboratory results, newsletters, study website, and retention surveys. Strategies for locating participants included frequent updates of contact information, sending registered letters, and searching medical and public records. RESULTS: At 12 and 24 months, 2426 and 2405 participants remained active, with vital status known for 98.7% and 97.3% and weight obtained for 95.2% and 92.2%, respectively. There were 148 missed visits (6.2%) at 24 months primarily because of inability to contact the participant. Only 15 (0.6%) active participants at 24 months missed all follow-up visits. Although 42 participants could not be located or contacted at 6 months, data were obtained for 23 (54.7%) of them at 12 months, and of the 52 participants who could not be located or contacted at 12 months, data were obtained for 18 (34.6%) at 24 months. CONCLUSION: Longitudinal studies provide the ability to evaluate long-term effects of bariatric surgical procedures. The retention achieved in LABS is superior to that of many published reports but requires extensive effort and resources. This report identifies useful retention strategies. Further research is needed to identify the efficacy and cost-effectiveness of specific retention strategies.

Path to bariatric nurse certification: the practice analysis.

BACKGROUND: In 2005, the American Society for Metabolic and Bariatric Surgery (ASMBS) nursing membership embarked on a journey to develop a specialty certification program for nurses caring for morbidly obese and bariatric surgical patients. In keeping with the certification industry best practices, a practice analysis study was conducted to create an empirically sound foundation for the new nursing specialty certification examination. METHODS: Task force meetings, subject-matter expert interviews, and an external review process were implemented to create a definition of the specialty in terms of 4 domains of practice, 45 nursing tasks, and 54 knowledge areas. The definition encompassed the work of bariatric nurse coordinators, bariatric program directors, and floor nurses caring for morbidly obese and bariatric surgical patients. A survey was administered to 1084 nurses practicing in the specialty to validate the domains, tasks, and knowledge. RESULTS: Some differences in the time spent in each of the domains and tasks were noted for the survey respondents in the different job roles. Nevertheless, the respondents for all job roles rated the domains and tasks moderately or highly important in optimizing the outcomes for morbidly obese and bariatric surgery patients. In addition, most respondents agreed that the 54 knowledge areas were acquired during the first 2 years of practice in the specialty. CONCLUSION: The survey results validated a specialized body of nursing knowledge rooted in the tasks that define professional practice. The results are being used to guide the development of a certification program for nurses practicing in the specialty and to provide guidance for education and training initiatives.