Renoprotective Effects of Metabolic Surgery Versus GLP1 Receptor Agonists on Progression of Kidney Impairment in Patients with Established Kidney Disease.

OBJECTIVE: To examine the renoprotective effects of metabolic surgery in patients with established chronic kidney disease (CKD). BACKGROUND: The impact of metabolic surgery compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with established CKD has not been fully characterized. METHODS: Patients with obesity (BMI ≥30 kg/m2), type 2 diabetes (T2DM), and baseline estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m² who underwent metabolic bariatric surgery at a large U.S. health system (2010-2017) were compared with nonsurgical patients who continuously received GLP-1RA. The primary end point was CKD progression, defined as decline of eGFR by ≥50% or to <15 mL/min/1.73 m2, initiation of dialysis, or kidney transplant. The secondary end point was the incident kidney failure (eGFR <15 mL/min/1.73 m2, dialysis, or kidney transplant) or all-cause mortality. RESULTS: 425 patients, including 183 patients in the metabolic surgery group and 242 patients in the GLP-1RA group, with a median follow-up of 5.8 years (IQR, 4.4-7.6) were analyzed. The cumulative incidence of the primary end point at 8-years was 21.7% (95% CI, 12.2-30.6) in the surgical group and 45.1% (95% CI, 27.7-58.4) in the nonsurgical group, with an adjusted hazard ratio of 0.40 (95% CI, 0.21-0.76), P=0.006. The cumulative incidence of the secondary composite end point at 8-years was 24.0% (95% CI, 14.1-33.2) in the surgical group and 43.8% (95% CI, 28.1-56.1) in the nonsurgical group, with an adjusted HR of 0.56 (95% CI, 0.31-0.99), P=0.048. CONCLUSIONS: Among patients with T2DM, obesity, and established CKD, metabolic surgery, compared with GLP-1RA, was significantly associated with a 60% lower risk of progression of kidney impairment and a 44% lower risk of kidney failure or death. Metabolic surgery should be considered as a therapeutic option for patients with CKD and obesity.

Insurance payor status and risk of major adverse cardiovascular and cerebrovascular events after metabolic and bariatric surgery.

BACKGROUND: Patients with Medicare/Medicaid insurance receive metabolic and bariatric surgery (MBS) at lower rates than privately insured (PI) patients. Although studies on some surgical procedures report that Medicare/Medicaid insurance confers increased postoperative complication rates and a longer length of stay, less is known about these outcomes after MBS. Among often-feared postoperative complications are major adverse cardiovascular and cerebrovascular events (MACEs). Although these events are rare after MBS, they have a significant impact on morbidity and mortality. OBJECTIVES: This study aimed to examine the effect of insurance payor status on MACEs after MBS. SETTING: The Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS). METHODS: HCUP-NIS was queried for cases including sleeve gastrectomy or Roux-en-Y gastric bypass between 2012 and 2019. Bivariate associations between patient-level factors and MACEs were assessed via Rao-Scott χ2 tests. Adjusted and unadjusted risks of insurance payor status for MACEs were evaluated using logistic regression. RESULTS: Incidence of MACEs was higher in both Medicare (.75% versus .11%; P < .001) and Medicaid (.15% versus .11%; P < .001) groups than in the PI group. After adjustment for high-risk demographics, high-risk co-morbidities, socioeconomic variables, and hospital factors, insurance status of Medicare (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.23, 2.07; P = .0026) or Medicaid (OR: 1.55, 95% CI: 1.12, 2.16; P = .0026) remained an independent risk factor for MACEs. CONCLUSIONS: Our findings underscore the significance of Medicaid/Medicare payor status as an independent predictor of postoperative MACEs in MBS. The results of this study can have a significant impact on deepening our understanding of socioeconomic and health system-related issues that can be targeted to improve outcomes in both MBS and other surgical specialties.

Limitations of the 2015-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database for emergency bariatric operations.

BACKGROUND: The Metabolic and Bariatric Surgery Quality Improvement Project (MBSAQIP) is the largest bariatric surgery-specific clinical data set. OBJECTIVES: In 2020, the definition of emergency cases was altered to include only revisional or conversion cases and not primary cases. The aim of this study was to examine how this change affects the utility of the data set for emergency case tracking. SETTING: MBSAQIP database. METHODS: Emergency cases were extracted from available MBSAQIP data (2015-2021). A comparison of co-morbidity profiles was done, specifically before and after the recent change to how "emergency" is defined in the data set. RESULTS: Eleven thousand and twenty-nine of the 1,048,575 total cases were coded as "emergency cases." From 2015 to 2019, 10,574 emergency cases were performed (∼2115 cases/yr), markedly decreasing in 2020 and 2021 to 455 cases (∼228 cases/yr). Before 2020, the most common procedures were the unlisted procedure of the stomach (45.14%, n = 3101), gastric band removal (25.3%, n = 2676), and reduction of internal hernia (11.8%, n = 1244). Between 2020 and 2021, this distribution changed with Roux-en-Y gastric bypass (RYGB), the most common emergency procedure (29.23%, n = 133). As expected from the change that captured only revisional cases, the average operative length was greater between 2020 and 2021 (127.6 versus 86.5 min). CONCLUSIONS: Capturable emergency cases declined in 2020, a trend related to changing the definition of emergency as part of MBSAQIP standards. This change excludes data on internal hernia reduction and does not likely reflect a real change in the prevalence of emergency bariatric cases. Because capture for emergency cases has diminished, so has any prior utility of using MBSAQIP data for studying emergency cases.

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.

New insights in the mechanisms of weight-loss maintenance: Summary from a Pennington symposium.

Obesity is a chronic disease that affects more than 650 million adults worldwide. Obesity not only is a significant health concern on its own, but predisposes to cardiometabolic comorbidities, including coronary heart disease, dyslipidemia, hypertension, type 2 diabetes, and some cancers. Lifestyle interventions effectively promote weight loss of 5% to 10%, and pharmacological and surgical interventions even more, with some novel approved drugs inducing up to an average of 25% weight loss. Yet, maintaining weight loss over the long-term remains extremely challenging, and subsequent weight gain is typical. The mechanisms underlying weight regain remain to be fully elucidated. The purpose of this Pennington Biomedical Scientific Symposium was to review and highlight the complex interplay between the physiological, behavioral, and environmental systems controlling energy intake and expenditure. Each of these contributions were further discussed in the context of weight-loss maintenance, and systems-level viewpoints were highlighted to interpret gaps in current approaches. The invited speakers built upon the science of obesity and weight loss to collectively propose future research directions that will aid in revealing the complicated mechanisms involved in the weight-reduced state.

Bariatric surgery alters mitochondrial function in gut mucosa.

BACKGROUND: The obesity pandemic has worsened global disease burden, including type 2 diabetes, cardiovascular disease, and cancer. Metabolic/bariatric surgery (MBS) is the most effective and durable obesity treatment, but the mechanisms underlying its long-term weight loss efficacy remain unclear. MBS drives substrate oxidation that has been linked to improvements in metabolic function and improved glycemic control that are potentially mediated by mitochondria-a primary site of energy production. As such, augmentation of intestinal mitochondrial function may drive processes underlying the systemic metabolic benefits of MBS. Herein, we applied a highly sensitive technique to evaluate intestinal mitochondrial function ex vivo in a mouse model of MBS. METHODS: Mice were randomized to surgery, sham, or non-operative control. A simplified model of MBS, ileal interposition, was performed by interposition of a 2-cm segment of terminal ileum into the proximal bowel 5 mm from the ligament of Treitz. After a four-week recovery period, intestinal mucosa of duodenum, jejunum, ileum, and interposed ileum were assayed for determination of mitochondrial respiratory function. Citrate synthase activity was measured as a marker of mitochondrial content. RESULTS: Ileal interposition was well tolerated and associated with modest body weight loss and transient hypophagia relative to controls. Mitochondrial capacity declined in the native duodenum and jejunum of animals following ileal interposition relative to controls, although respiration remained unchanged in these segments. Similarly, ileal interposition lowered citrate synthase activity in the duodenum and jejunum following relative to controls but ileal function remained constant across all groups. CONCLUSION: Ileal interposition decreases mitochondrial volume in the proximal intestinal mucosa of mice. This change in concentration with preserved respiration suggests a global mucosal response to segment specific nutrition signals in the distal bowel. Future studies are required to understand the causes underlying these mitochondrial changes.

The Vagus Nerve Mediates Gut-Brain Response to Duodenal Nutrient Administration.

BACKGROUND: Obesity contributes significant disease burden worldwide, including diabetes, cardiovascular disease, and cancer. While bariatric surgery is the most effective and durable obesity treatment, the mechanisms underlying its effects remain unknown. Although neuro-hormonal mechanisms have been suspected to mediate at least some of the gut-brain axis changes following bariatric surgery, studies examining the intestine and its regionally specific post-gastric alterations to these signals remain unclear. MATERIALS AND METHODS: Vagus nerve recording was performed following the implantation of duodenal feeding tubes in mice. Testing conditions and measurements were made under anesthesia during baseline, nutrient or vehicle solution delivery, and post-delivery. Solutions tested included water, glucose, glucose with an inhibitor of glucose absorption (phlorizin), and a hydrolyzed protein solution. RESULTS: Vagus nerve signaling was detectable from the duodenum and exhibited stable baseline activity without responding to osmotic pressure gradients. Duodenal-delivered glucose and protein robustly increased vagus nerve signaling, but increased signaling was abolished during the co-administration of glucose and phlorizin. DISCUSSION: Gut-brain communication via the vagus nerve emanating from the duodenum is nutrient sensitive and easily measurable in mice. Examination of these signaling pathways may help elucidate how the nutrient signals from the intestine are altered when applied to obesity and bariatric surgery mouse models. Future studies will address quantifying the changes in neuroendocrine nutrient signals in health and obesity, with specific emphasis on identifying the changes associated with bariatric surgery and other gastrointestinal surgery.

Remission with an Intervention: Is Metabolic Surgery the Ultimate Solution?

Long-term remission of type 2 diabetes following lifestyle intervention or pharmacotherapy, even in patients with mild disease, is rare. Long-term remission following metabolic surgery however, is common and occurs in 23% to 98% depending on disease severity and type of surgery. Remission after surgery is associated with excellent glycemic control without reliance on pharmacotherapy, improvements in quality of life, and major reductions in microvascular and macrovascular complications. For patients with type 2 diabetes, early intervention with metabolic surgery, when beta cell function still remains intact, provides the greatest probability of long-term remission as high as 90% or more.

Effect of high-risk factors on postoperative major adverse cardiovascular and cerebrovascular events trends following bariatric surgery in the United States from 2012 to 2019.

BACKGROUND: Recent examination of trends in postoperative major adverse cardiovascular and cerebrovascular events (MACE) following bariatric surgery, including accredited and nonaccredited centers, and the factors affecting those trends, is lacking. OBJECTIVES: The objective of this study was to evaluate current trends for postoperative MACE after bariatric surgery in both accredited and nonaccredited centers and the factors affecting these trends. SETTING: This retrospective study was conducted using National Inpatient Sample database from 2012 to 2019. METHODS: All patients who underwent inpatient laparoscopic sleeve gastrectomy (LSG), open sleeve gastrectomy (SG), laparoscopic Roux-en-Y gastric bypass (LRYGB), and open Roux-en-Y gastric bypass (RYGB) were examined. Composite MACE (acute myocardial infarction, cardiac arrest, acute stroke, and in-hospital death during bariatric surgery hospitalization) was calculated and analyzed over time along with patient demographic and co-morbid diseases using survey-weighted logistic regression. RESULTS: MACE incidence was lowest for LSG (0.07%), followed by LRYGB (0.16%), SG (3.47%), and RYBG (3.51%). Open procedure, increasing age, male sex, body mass index ≥50, coronary artery disease, congestive heart failure, and chronic kidney disease were independent predictors for increased MACE risk. MACE incidence increased over time for SG (odds ratio [OR] 1.25 [1.16, 1.34]; P < .0001) and RYGB (OR 1.14 [1.06, 1.22]; P = .0004) but decreased for LRYGB (OR 0.93 [0.87, 1] P = .06). After adjustment for high-risk covariates, increased MACE trend seen over time was attenuated in SG (OR 1.13 [1.04-1.22]; P = .005) and RYGB (OR 1.04 [0.96-1.12]; P = .36), while there was minimal effect of these high-risk covariates on MACE trend over time in LSG and LRYGB. CONCLUSIONS: MACE following LSG and LRYGB is rare, occurring in 0.1% of patients. Persistently increasing high-risk conditions and demographics has had minimal effect on MACE over time for LSG and LRYGB but has had significant effect on MACE trend over time in SG and RYGB.

Obstacles and opportunities in managing coexisting obesity and CKD: Report of a scientific workshop cosponsored by the National Kidney Foundation and The Obesity Society.

The National Kidney Foundation (NKF) and The Obesity Society (TOS) cosponsored a multispecialty international workshop in April 2021 to advance the understanding and management of obesity in adults with chronic kidney disease (CKD). The underlying rationale for the workshop was the accumulating evidence that obesity is a major contributor to CKD and adverse outcomes in individuals with CKD, and that effective treatment of obesity, including lifestyle intervention, weight loss medications, and metabolic surgery, can have beneficial effects. The attendees included a range of experts in the areas of kidney disease, obesity medicine, endocrinology, diabetes, bariatric/metabolic surgery, endoscopy, transplant surgery, and nutrition, as well as patients with obesity and CKD. The group identified strategies to increase patient and provider engagement in obesity management, outlined a collaborative action plan to engage nephrologists and obesity medicine experts in obesity management, and identified research opportunities to address gaps in knowledge about the interaction between obesity and kidney disease. The workshop's conclusions help lay the groundwork for development of an effective, scientifically based, and multidisciplinary approach to the management of obesity in people with CKD.

Obstacles and Opportunities in Managing Coexisting Obesity and CKD: Report of a Scientific Workshop Cosponsored by the National Kidney Foundation and The Obesity Society.

The National Kidney Foundation (NKF) and The Obesity Society (TOS) cosponsored a multispecialty international workshop in April 2021 to advance the understanding and management of obesity in adults with chronic kidney disease (CKD). The underlying rationale for the workshop was the accumulating evidence that obesity is a major contributor to CKD and adverse outcomes in individuals with CKD, and that effective treatment of obesity, including lifestyle intervention, weight loss medications, and metabolic surgery, can have beneficial effects. The attendees included a range of experts in the areas of kidney disease, obesity medicine, endocrinology, diabetes, bariatric/metabolic surgery, endoscopy, transplant surgery, and nutrition, as well as patients with obesity and CKD. The group identified strategies to increase patient and provider engagement in obesity management, outlined a collaborative action plan to engage nephrologists and obesity medicine experts in obesity management, and identified research opportunities to address gaps in knowledge about the interaction between obesity and kidney disease. The workshop's conclusions help lay the groundwork for development of an effective, scientifically based, and multidisciplinary approach to the management of obesity in people with CKD.

Risk of non-hormonal cancer after bariatric surgery: meta-analysis of retrospective observational studies.

BACKGROUND: Obesity is associated with an increased incidence of at least 13 types of cancer. Although bariatric surgery has been associated with a reduced risk of hormonal cancers, data for non-hormonal cancers are scarce. The aim of this study was to evaluate the effect of bariatric surgery on the incidence of non-hormonal cancers. METHODS: Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles between 1984 and 2018, following the PRISMA system. Meta-analysis was conducted using a random-effect model with subgroup analysis by procedure and cancer type. RESULTS: From 2526 studies screened, 15 were included. There were a total of 18 583 477 patients, 947 787 in the bariatric group and 17 635 690 in the control group. In comparison to the non-surgical group, the bariatric group had a lower incidence of cancer (OR .65 (95 per cent c.i. 0.53 to 0.80); P < 0.002). In the subgroup analysis, Roux-en-Y gastric bypass and sleeve gastrectomy were associated with decreased risk of developing cancer, while no difference was observed with adjustable gastric banding. When evaluated by cancer type, liver (OR 0.417 (95 per cent c.i. 0.323 to 0.538)), colorectal (OR 0.64 (95 per cent c.i. 0.49 to 0.84)), kidney and urinary tract cancer (OR 0.77 (95 per cent c.i. 0.72 to 0.83)), oesophageal (OR 0.60 (95 per cent c.i. 0.43 to 0.85)), and lung cancer (OR 0.796 (95 per cent c.i. 0.45 to 0.80)) also presented a lower cancer incidence in the bariatric group. CONCLUSION: Bariatric surgery is related to an almost 50 per cent reduction in the risk of non-hormonal cancers.

The role of bariatric and metabolic surgery in the development, diagnosis, and treatment of endometrial cancer.

The obesity pandemic continues to contribute to a worsening burden of disease worldwide. The link between obesity and diseases such as diabetes, cardiovascular disease, and cancer has been well established, yet most patients living with obesity remain untreated or undertreated. Metabolic and bariatric surgery is the most effective and durable treatment for obesity, is safe, and may have a protective benefit with respect to cancer incidence. In this review, an overview of the link between obesity, metabolic surgery, and cancer is discussed with emphasis on indications for endometrial cancer, the malignancy most strongly associated with obesity. Considerable evidence from retrospective and prospective cohort studies supports a decreased risk of endometrial cancer in patients with obesity who undergo bariatric surgery compared with nonsurgical controls. Survivors of endometrial cancer are at increased risk of poor health outcomes associated with obesity, and women with endometrial cancer are more likely to die of cardiovascular disease and other obesity-related illnesses than of the malignancy itself. Recent advances in anticancer drug therapies have targeted pathways that may also be therapeutically altered with metabolic surgery. Metabolic surgery has significant potential to enter the treatment paradigm for endometrial cancer, and gynecologic oncologist visits present an opportunity to identify patients who may benefit the most.

Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity.

Importance: Obesity increases the incidence and mortality from some types of cancer, but it remains uncertain whether intentional weight loss can decrease this risk. Objective: To investigate whether bariatric surgery is associated with lower cancer risk and mortality in patients with obesity. Design, Setting, and Participants: In the SPLENDID (Surgical Procedures and Long-term Effectiveness in Neoplastic Disease Incidence and Death) matched cohort study, adult patients with a body mass index of 35 or greater who underwent bariatric surgery at a US health system between 2004 and 2017 were included. Patients who underwent bariatric surgery were matched 1:5 to patients who did not undergo surgery for their obesity, resulting in a total of 30 318 patients. Follow-up ended in February 2021. Exposures: Bariatric surgery (n = 5053), including Roux-en-Y gastric bypass and sleeve gastrectomy, vs nonsurgical care (n = 25 265). Main Outcomes and Measures: Multivariable Cox regression analysis estimated time to incident obesity-associated cancer (a composite of 13 cancer types as the primary end point) and cancer-related mortality. Results: The study included 30 318 patients (median age, 46 years; median body mass index, 45; 77% female; and 73% White) with a median follow-up of 6.1 years (IQR, 3.8-8.9 years). The mean between-group difference in body weight at 10 years was 24.8 kg (95% CI, 24.6-25.1 kg) or a 19.2% (95% CI, 19.1%-19.4%) greater weight loss in the bariatric surgery group. During follow-up, 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group had an incident obesity-associated cancer (incidence rate of 3.0 events vs 4.6 events, respectively, per 1000 person-years). The cumulative incidence of the primary end point at 10 years was 2.9% (95% CI, 2.2%-3.6%) in the bariatric surgery group and 4.9% (95% CI, 4.5%-5.3%) in the nonsurgical control group (absolute risk difference, 2.0% [95% CI, 1.2%-2.7%]; adjusted hazard ratio, 0.68 [95% CI, 0.53-0.87], P = .002). Cancer-related mortality occurred in 21 patients in the bariatric surgery group and 205 patients in the nonsurgical control group (incidence rate of 0.6 events vs 1.2 events, respectively, per 1000 person-years). The cumulative incidence of cancer-related mortality at 10 years was 0.8% (95% CI, 0.4%-1.2%) in the bariatric surgery group and 1.4% (95% CI, 1.1%-1.6%) in the nonsurgical control group (absolute risk difference, 0.6% [95% CI, 0.1%-1.0%]; adjusted hazard ratio, 0.52 [95% CI, 0.31-0.88], P = .01). Conclusions and Relevance: Among adults with obesity, bariatric surgery compared with no surgery was associated with a significantly lower incidence of obesity-associated cancer and cancer-related mortality.

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.

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.

Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes.

Improvement of glucose levels into the normal range can occur in some people living with diabetes, either spontaneously or after medical interventions, and in some cases can persist after withdrawal of glucose-lowering pharmacotherapy. Such sustained improvement may now be occurring more often due to newer forms of treatment. However, terminology for describing this process and objective measures for defining it are not well established, and the long-term risks versus benefits of its attainment are not well understood. To update prior discussions of this issue, an international expert group was convened by the American Diabetes Association to propose nomenclature and principles for data collection and analysis, with the goal of establishing a base of information to support future clinical guidance. This group proposed "remission" as the most appropriate descriptive term, and HbA1c < 6.5% (48 mmol/mol) measured at least 3 months after cessation of glucose-lowering pharmacotherapy as the usual diagnostic criterion. The group also made suggestions for active observation of individuals experiencing a remission and discussed further questions and unmet needs regarding predictors and outcomes of remission.

Consensus report: Definition and interpretation of remission in type 2 diabetes.

Improvement of glucose levels into the normal range can occur in some people living with diabetes, either spontaneously or after medical interventions, and in some cases can persist after withdrawal of glucose-lowering pharmacotherapy. Such sustained improvement may now be occurring more often due to newer forms of treatment. However, terminology for describing this process and objective measures for defining it are not well established, and the long-term risks versus benefits of its attainment are not well understood. To update prior discussions of this issue, an international expert group was convened by the American Diabetes Association to propose nomenclature and principles for data collection and analysis, with the goal of establishing a base of information to support future clinical guidance. This group proposed "remission" as the most appropriate descriptive term, and HbA1c <6.5% (48 mmol/mol) measured at least 3 months after cessation of glucose-lowering pharmacotherapy as the usual diagnostic criterion. The group also made suggestions for active observation of individuals experiencing a remission and discussed further questions and unmet needs regarding predictors and outcomes of remission.

Association of Bariatric Surgery With Major Adverse Liver and Cardiovascular Outcomes in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis.

IMPORTANCE: No therapy has been shown to reduce the risk of serious adverse outcomes in patients with nonalcoholic steatohepatitis (NASH). OBJECTIVE: To investigate the long-term relationship between bariatric surgery and incident major adverse liver outcomes and major adverse cardiovascular events (MACE) in patients with obesity and biopsy-proven fibrotic NASH without cirrhosis. DESIGN, SETTING, AND PARTICIPANTS: In the SPLENDOR (Surgical Procedures and Long-term Effectiveness in NASH Disease and Obesity Risk) study, of 25 828 liver biopsies performed at a US health system between 2004 and 2016, 1158 adult patients with obesity were identified who fulfilled enrollment criteria, including confirmed histological diagnosis of NASH and presence of liver fibrosis (histological stages 1-3). Baseline clinical characteristics, histological disease activity, and fibrosis stage of patients who underwent simultaneous liver biopsy at the time of bariatric surgery were balanced with a nonsurgical control group using overlap weighting methods. Follow-up ended in March 2021. EXPOSURES: Bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy) vs nonsurgical care. MAIN OUTCOMES AND MEASURES: The primary outcomes were the incidence of major adverse liver outcomes (progression to clinical or histological cirrhosis, development of hepatocellular carcinoma, liver transplantation, or liver-related mortality) and MACE (a composite of coronary artery events, cerebrovascular events, heart failure, or cardiovascular death), estimated using the Firth penalized method in a multivariable-adjusted Cox regression analysis framework. RESULTS: A total of 1158 patients (740 [63.9%] women; median age, 49.8 years [IQR, 40.9-57.9 years], median body mass index, 44.1 [IQR, 39.4-51.4]), including 650 patients who underwent bariatric surgery and 508 patients in the nonsurgical control group, with a median follow-up of 7 years (IQR, 4-10 years) were analyzed. Distribution of baseline covariates, including histological severity of liver injury, was well-balanced after overlap weighting. At the end of the study period in the unweighted data set, 5 patients in the bariatric surgery group and 40 patients in the nonsurgical control group experienced major adverse liver outcomes, and 39 patients in the bariatric surgery group and 60 patients in the nonsurgical group experienced MACE. Among the patients analyzed with overlap weighting methods, the cumulative incidence of major adverse liver outcomes at 10 years was 2.3% (95% CI, 0%-4.6%) in the bariatric surgery group and 9.6% (95% CI, 6.1%-12.9%) in the nonsurgical group (adjusted absolute risk difference, 12.4% [95% CI, 5.7%-19.7%]; adjusted hazard ratio, 0.12 [95% CI, 0.02-0.63]; P = .01). The cumulative incidence of MACE at 10 years was 8.5% (95% CI, 5.5%-11.4%) in the bariatric surgery group and 15.7% (95% CI, 11.3%-19.8%) in the nonsurgical group (adjusted absolute risk difference, 13.9% [95% CI, 5.9%-21.9%]; adjusted hazard ratio, 0.30 [95% CI, 0.12-0.72]; P = .007). Within the first year after bariatric surgery, 4 patients (0.6%) died from surgical complications, including gastrointestinal leak (n = 2) and respiratory failure (n = 2). CONCLUSIONS AND RELEVANCE: Among patients with NASH and obesity, bariatric surgery, compared with nonsurgical management, was associated with a significantly lower risk of incident major adverse liver outcomes and MACE.