Remission of Obesity-Related Sleep Apnea and Its Effect on Mortality and Cardiovascular Events After Metabolic and Bariatric Surgery: A Propensity Matched Cohort Study.

BACKGROUND: While obstructive sleep apnea (OSA) is common among patients with obesity and linked to cardiovascular disease, there is a lack of studies evaluating the effects of reaching remission from OSA after metabolic and bariatric surgery (MBS). STUDY DESIGN: A registry-based nationwide study including patients operated with sleeve gastrectomy or Roux-en-Y gastric bypass from 2007 until 2019 in Sweden. Patients who reached remission of OSA were compared to those who did not reach remission, and a propensity score matched control group of patients without OSA at the time of operation. Main outcome was overall mortality, secondary outcome was major cardiovascular events (MACE). RESULTS: In total, 5892 patients with OSA and 11,552 matched patients without OSA completed a 1-year follow-up and were followed for a median of 6.8 years. Remission of OSA was seen for 4334 patients (74%). Patients in remission had a lower risk for overall mortality (cumulative incidence 6.0% v. 9.1%;p<0.001) and MACE (cumulative incidence 3.4% vs 5.8%;p<0.001) at 10-years after operation compared to those who did not reach remission. The risk was similar to that of the control group without OSA at baseline (cumulative incidence for mortality 6.0%, p=0.493, for MACE 3.7%, p=0.251). CONCLUSION: The remission rate of OSA was high after MBS. This was in turn associated with reduced risk for death and MACE compared to patients who did not achieve remission reaching a similar risk seen among patients without OSA at baseline. A diligent follow-up of patients who do not reach remission remains important.

Comparison of Sleeve Gastrectomy vs Roux-en-Y Gastric Bypass: A Randomized Clinical Trial.

Importance: Laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) are widely used bariatric procedures for which comparative efficacy and safety remain unclear. Objective: To compare perioperative outcomes in SG and RYGB. Design, Setting, and Participants: In this registry-based, multicenter randomized clinical trial (Bypass Equipoise Sleeve Trial), baseline and perioperative data for patients undergoing bariatric surgery from October 6, 2015, to March 31, 2022, were analyzed. Patients were from university, regional, county, and private hospitals in Sweden (n = 20) and Norway (n = 3). Adults (aged ≥18 years) eligible for bariatric surgery with body mass indexes (BMIs; calculated as weight in kilograms divided by height in meters squared) of 35 to 50 were studied. Interventions: Laparoscopic SG or RYGB. Main Outcomes and Measures: Perioperative complications were analyzed as all adverse events and serious adverse events (Clavien-Dindo grade >IIIb). Ninety-day mortality was also assessed. Results: A total of 1735 of 14 182 eligible patients (12%; 1282 [73.9%] female; mean (SD) age, 42.9 [11.1] years; mean [SD] BMI, 40.8 [3.7]) were included in the study. Patients were randomized and underwent SG (n = 878) or RYGB (n = 857). The mean (SD) operating time was shorter in those undergoing SG vs RYGB (47 [18] vs 68 [25] minutes; P < .001). The median (IQR) postoperative hospital stay was 1 (1-1) day in both groups. The 30-day readmission rate was 3.1% after SG and 4.0% after RYGB (P = .33). There was no 90-day mortality. The 30-day incidence of any adverse event was 40 (4.6%) and 54 (6.3%) in the SG and RYGB groups, respectively (odds ratio, 0.71; 95% CI, 0.47-1.08; P = .11). Corresponding figures for serious adverse events were 15 (1.7%) for the SG group and 23 (2.7%) for the RYGB group (odds ratio, 0.63; 95% CI, 0.33-1.22; P = .19). Conclusions and Relevance: This randomized clinical trial of 1735 patients undergoing primary bariatric surgery found that both SG and RYGB were performed with a low perioperative risk without clinically significant differences between groups. Trial Registration: ClinicalTrials.gov Identifier: NCT02767505.

Results from the Scandinavian Obesity Surgery Registry: A narrative review.

In 2007, the Scandinavian Obesity Surgery Registry (SOReg) was started by the profession to monitor the results of bariatric surgery and to provide a high-quality database for research. In the end of August 2023, SOReg contains 88,379 patients (body mass index [BMI] 41.7 kg/m2 , 41.2 years, 77.1% females, gastric bypass 76.8%). In this narrative review, we demonstrate that preoperative weight loss is of value and that the laparoscopic double omega-loop technique is highly suitable for gastric bypass. Closing the mesenteric openings is, however, important. Swedish bariatric surgery has low mortality, and our results are comparative to those of other countries. Significant long-term improvements are found in common obesity-related diseases such as diabetes, hypertension, and sleep apnea. Furthermore, the risk for cardiac failure and major adverse cardiovascular events is significantly reduced. Pregnancy-related outcomes are also improved. Gastric bypass results in significant improvements in quality of life and seems to be cost saving. We have revealed that low socioeconomic status is associated with reduced chance of undergoing bariatric surgery and inferior outcomes. Of note, we have performed several randomized clinical trials within the registry database. In conclusion, high-quality national registry databases, such as SOReg, are important for maintaining high-quality care and present a platform for extensive research.

Impact of socioeconomic status on new chronic opioid use after gastric bypass surgery.

BACKGROUND: Socioeconomic status may influence weight loss, postoperative complications, and health-related quality of life after bariatric surgery. Chronic use of opioid analgesics is a known risk after bariatric surgery, but whether socioeconomic factors are associated with new chronic use of opioid analgesics has not been investigated in depth. OBJECTIVES: The aim of this study was to identify socioeconomic factors associated with the development of new chronic use of opioid analgesics after gastric bypass surgery. SETTING: All hospitals performing bariatric surgery in Sweden. METHODS: This was a retrospective cohort study with prospectively collected data including all primary gastric bypass procedures in Sweden between 2007 and 2015. Data were collected from the Scandinavian Obesity Surgery Registry, the Swedish Prescribed Drug Register, and Statistics Sweden. The primary outcome was new chronic opioid use. RESULTS: Of the 44,671 participants, 1438 patients became new chronic opioid users. Longer education (secondary education; odds ratio [OR] = .71; 95% CI, .62-.81) or higher education (OR = .45; 95% CI, .38-.53), higher disposable income (20th-50th percentile: OR = .75; 95% CI, .66-.85; 50th-80th percentile: OR = .50; 95% CI, .43-.58; and the highest 80th percentile: OR = .40; 95% CI, .32-.51) were significantly associated with lower risk for new chronic opioid use. Being a second-generation immigrant (OR = 1.54; 95% CI, 1.24-1.90), being on a disability pension or early retirement (OR = 3.04; 95% CI, 2.67-3.45), receiving social benefits (OR = 1.88; 95% CI, 1.59-2.22), being unemployed for <100 days (OR = 1.25; 95% CI, 1.08-1.45), being unemployed for >100 days (OR = 1.41; 95% CI, 1.16-1.71), and being divorced or a widow or widower (OR = 1.35; 95% CI, 1.17-1.55) were significantly associated with a higher risk for chronic opioid use. CONCLUSION: Given that long-term opioid use has detrimental effects after bariatric surgery, it is important that information and follow-up are optimized for patients with shorter education, lower income, and disability pension or early retirement because they are at an increased risk of new chronic opioid analgesics use.

Human resident liver myeloid cells protect against metabolic stress in obesity.

Although multiple populations of macrophages have been described in the human liver, their function and turnover in patients with obesity at high risk of developing non-alcoholic fatty liver disease (NAFLD) and cirrhosis are currently unknown. Herein, we identify a specific human population of resident liver myeloid cells that protects against the metabolic impairment associated with obesity. By studying the turnover of liver myeloid cells in individuals undergoing liver transplantation, we find that liver myeloid cell turnover differs between humans and mice. Using single-cell techniques and flow cytometry, we determine that the proportion of the protective resident liver myeloid cells, denoted liver myeloid cells 2 (LM2), decreases during obesity. Functional validation approaches using human 2D and 3D cultures reveal that the presence of LM2 ameliorates the oxidative stress associated with obese conditions. Our study indicates that resident myeloid cells could be a therapeutic target to decrease the oxidative stress associated with NAFLD.

Long-term Safety and Efficacy of Closure of Mesenteric Defects in Laparoscopic Gastric Bypass Surgery: A Randomized Clinical Trial.

Importance: Short-term and midterm data suggest that mesenteric defects closure during laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery reduces the risk of internal herniation with small bowel obstruction (SBO) but may increase risk of kinking of the jejunojejunostomy in the early postoperative period. However, to our knowledge, there are no clinical trials reporting long-term results from this intervention in terms of risk for SBO or opioid use. Objective: To evaluate long-term safety and efficacy outcomes of closure of mesenteric defects during LRYGB. Design, Setting, and Participants: This randomized clinical trial with a 2-arm, parallel, open-label design included patients with severe obesity scheduled for LRYGB bariatric surgery at 12 centers in Sweden from May 1, 2010, through November 14, 2011, with 10 years of follow-up after the intervention. Interventions: During the operation, patients were randomly assigned 1:1 to closure of mesenteric defects beneath the jejunojejunostomy and at the Petersen space using nonabsorbable running sutures during LRYGB or to nonclosure. Main Outcome and Measures: The primary outcome was reoperation for SBO. New incident, chronic opioid use was a secondary end point as a measure of harm. Results: A total of 2507 patients (mean [SD] age, 41.7 [10.7] years; 1863 female [74.3%]) were randomly assigned to closure of mesenteric defects (n = 1259) or nonclosure (n = 1248). After censoring for death and emigration, 1193 patients in the closure group (94.8%) and 1198 in the nonclosure group (96.0%) were followed up until the study closed. Over a median follow-up of 10 years (IQR, 10.0-10.0 years), a reoperation for SBO from day 31 to 10 years after surgery was performed in 185 patients with nonclosure (10-year cumulative incidence, 14.9%; 95% CI, 13.0%-16.9%) and in 98 patients with closure (10-year cumulative incidence, 7.8%; 95% CI, 6.4%-9.4%) (subhazard ratio [SHR], 0.42; 95% CI, 0.32-0.55). New incident chronic opioid use was seen among 175 of 863 opioid-naive patients with nonclosure (10-year cumulative incidence, 20.4%; 95% CI, 17.7%-23.0%) and 166 of 895 opioid-naive patients with closure (10-year cumulative incidence, 18.7%; 95% CI, 16.2%-21.3%) (SHR, 0.90; 95% CI, 0.73-1.11). Conclusions and Relevance: This randomized clinical trial found long-term reduced risk of SBO after mesenteric defects closure in LRYGB. The findings suggest that routine use of this procedure during LRYGB should be considered. Trial Registration: ClinicalTrials.gov Identifier: NCT01137201.

Incidence of Kidney Stones After Metabolic and Bariatric Surgery-Data from the Scandinavian Obesity Surgery Registry.

PURPOSE: Obesity is associated with increased incidence of kidney stones, a risk further increased by metabolic and bariatric surgery, particularly after procedures with a malabsorptive component. However, there is a paucity in reports on baseline risk factor and on larger population-based cohorts. The objective was to evaluate incidence and risk factors for kidney stones after bariatric surgery by comparing them to an age-, sex-, and geographically matched cohort from the normal population. MATERIAL AND METHODS: Patients operated with primary Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or biliopancreatic diversion with duodenal switch (BPD-DS) from 2007 until 2017 within the Scandinavian Obesity Surgery registry were matched 1:10 to controls from the normal population. Hospital admission or outpatient visits due to kidney stones registered in the National Patient Registry were considered as endpoint. RESULTS: The study included 58,366 surgical patients (mean age 41.0±11.1, BMI 42.0±5.68, 76% women) with median follow-up time 5.0 [IQR 2.9-7.0] years and 583,660 controls. All surgical procedures were associated with a significantly increased risk for kidney stones (RYGB, HR 6.16, [95% CI 5.37-7.06]; SG, HR 6.33, [95% CI 3.57-11.25]; BPD/DS, HR 10.16, [95% CI 2.94-35.09]). Higher age, type 2 diabetes hypertension at baseline, and a preoperative history of kidney stones were risk factors for having a postoperative diagnosis of kidney stones. CONCLUSION: Primary RYGB, SG, and BPD/DS were all associated with a more than sixfold increased risk for postoperative kidney stones. The risk increased with advancing age, two common obesity-related conditions, and among patients with preoperative history of kidney stones.

Oxygen saturation in intraosseous sternal blood measured by CO-oximetry and evaluated non-invasively during hypovolaemia and hypoxia - a porcine experimental study.

PURPOSE: This study intended to determine, and non-invasively evaluate, sternal intraosseous oxygen saturation (SsO2) and study its variation during provoked hypoxia or hypovolaemia. Furthermore, the relation between SsO2 and arterial (SaO2) or mixed venous oxygen saturation (SvO2) was investigated. METHODS: Sixteen anaesthetised male pigs underwent exsanguination to a mean arterial pressure of 50 mmHg. After resuscitation and stabilisation, hypoxia was induced with hypoxic gas mixtures (air/N2). Repeated blood samples from sternal intraosseous cannulation were compared to arterial and pulmonary artery blood samples. Reflection spectrophotometry measurements by a non-invasive sternal probe were performed continuously. RESULTS: At baseline SaO2 was 97.0% (IQR 0.2), SsO2 73.2% (IQR 19.6) and SvO2 52.3% (IQR 12.4). During hypovolaemia, SsO2 and SvO2 decreased to 58.9% (IQR 16.9) and 38.1% (IQR 12.5), respectively, p < 0.05 for both, whereas SaO2 remained unaltered (p = 0.44). During hypoxia all saturations decreased; SaO2 71.5% (IQR 5.2), SsO2 39.0% (IQR 6.9) and SvO2 22.6% (IQR 11.4) (p < 0.01), respectively. For hypovolaemia, the sternal probe red/infrared absorption ratio (SQV) increased significantly from baseline (indicating a reduction in oxygen saturation) + 5.1% (IQR 7.4), p < 0.001 and for hypoxia + 19.9% (IQR 14.8), p = 0.001, respectively. CONCLUSION: Sternal blood has an oxygen saturation suggesting a mixture of venous and arterial blood. Changes in SsO2 relate well with changes in SvO2 during hypovolaemia or hypoxia. Further studies on the feasibility of using non-invasive measurement of changes in SsO2 to estimate changes in SvO2 are warranted.

Major adverse cardiovascular events among patients with type-2 diabetes, a nationwide cohort study comparing primary metabolic and bariatric surgery to GLP-1 receptor agonist treatment.

BACKGROUND: Glucagon-like Peptide-1 receptor agonists (GLP-1 RA) and metabolic and bariatric surgery (MBS) both improve cardiovascular outcomes in patients with severe obesity and type-2 diabetes (T2D). The aim of the present study was to assess the impact of MBS on major cardiovascular adverse events (MACE) in patients with severe obesity and T2D compared to patients with T2D treated with GLP-1 RA. SUBJECTS AND METHODS: In this propensity score matched cohort study on nationwide data, patients with T2D and severe obesity who underwent MBS in Sweden from 2007 until 2019 were identified from the Scandinavian Obesity Surgery Registry and matched to a non-surgical group with T2D treated with GLP-1 RA (81.7% liraglutide, 9.0% dulaglutide, 6.0% exenatide, 1.6% lixisenatide and 0.8% semaglutide) from the general population using generalized linear model. Major outcome was MACE (hospitalization for acute coronary syndrome or cerebrovascular event or all-cause death), evaluated with multivariable Cox regression. RESULTS: In total 2161 patients (obesity class I (10.2%), class II (40.3%), class III (49.5%)) were matched to 2161 non-surgical patients (mean age 51.1 ± 9.29 vs 51.5 ± 8.92 years, 64.8% vs. 64.4% women, with mean number of diabetes drugs of 2.5 ± 0.89 vs 2.6 ± 0.87, a mean duration of diabetes of 6.0 ± 4.15 vs 6.0 ± 4.51 years with 44.2% vs. 42.8% being treated with insulin at baseline). During the study period, 113 patients (8-year cumulative incidence 9.3%) compared to 130 non-surgical patients (8-year cumulative incidence 11.3%) suffered from MACE or all-cause mortality (HR 0.76, 95%CI 0.59-0.98), and 69 patients (8-year cumulative incidence 5.1%) compared to 92 non-surgical patients (8-year cumulative incidence 7.6%) suffered from a non-fatal MACE (HR 0.68, 95%CI 0.49-0.93). CONCLUSION: In this matched cohort study, MBS was associated with lower risk for MACE compared to treatment with early GLP-1 RA in patients with T2D.

Incidence of self-harm after bariatric surgery: A nationwide registry-based matched cohort study.

The aims of this study were to evaluate the longitudinal risk of self-harm and the risk factors for self-harm after bariatric surgery in patients and control subjects without prior self-harm. This observational cohort study was based on prospectively registered data. Patients 18-70 years at time of surgery, body mass index (BMI) > 30 kg/m2 , who underwent a primary Roux-en-Y gastric bypass (RYGB) procedure or a primary sleeve gastrectomy between 2007 and 2019 were considered for inclusion. All patients who met the inclusion criteria were matched 1:10 to the general population in Sweden (69 492 patients vs. 694 920 controls). After excluding patients and controls with previous self-harm, a self-harm event occurred in 1408 patients in the surgical group (incidence rate (IR) 3.54/1000 person-years, 95% confidence interval (CI) 3.36-3.73) versus in 3162 patients in the control group (IR 0.81/1000 person-years, 95% CI 0.78-0.84), with a hazard ratio (HR) of 4.38 (95% CI 4.11-4.66, p < .001). Median follow-up time was 6.1 years. Risk factors were younger age, lower BMI, cardiovascular, and chronic obstructive pulmonary disease, all aspects of psychiatric comorbidities (except neuropsychiatric disorder), lower socioeconomic status, RYGB, lower health-related quality of life, lower postoperative weight loss, and not attending postoperative follow-up visits. Self-harm is clearly higher after bariatric surgery than in the general population. A qualitative follow-up may be particularly important for patients at increased risk.

Association between attention deficit hyperactivity disorder and outcomes after metabolic and bariatric surgery: a nationwide propensity-matched cohort study.

BACKGROUND: The risks and benefits of metabolic and bariatric surgery for patients with attention deficit hyperactivity disorder (ADHD) remain to be investigated. OBJECTIVE: The aim of this study was to assess short- and long-term outcomes after metabolic and bariatric surgery in patients with previous ADHD compared with matched control individuals. SETTING: Registry based. METHODS: This 2-staged matched-cohort study included all adults with a body mass index of ≥30 kg/m2 who underwent primary Roux-en-Y gastric bypass or sleeve gastrectomy from 2007 until 2017 registered in the Scandinavian Obesity Surgery Registry. Patients with prescribed medication for ADHD were matched with control individuals without ADHD with a follow-up of up to 11 years after surgery. RESULTS: Among 1431 patients with ADHD and 2862 control individuals (mean body mass index, 42 kg/m2; mean age, 35 years), no difference in weight loss or follow-up attendance over 2 years was seen. ADHD was associated with a higher risk for early postoperative complications (odds ratio [OR] = 1.31; 95% confidence interval [CI], 1.05-1.63), self-harm (hazards ratio [HR] = 1.39; 95% CI, 1.11-1.75), and substance abuse (HR = 1.34; 95% CI, 1.16-1.55), while associations with overall mortality (HR = 1.42; 95% CI, .99-2.03), major adverse cardiovascular and cerebrovascular events (HR = 1.93; 95% CI, .98-3.83), and effects on obesity-related diseases were uncertain. ADHD was associated with a lower health-related quality of life in all aspects before surgery. These differences increased for mental and obesity-related aspects but remained unchanged over time for physical aspects. CONCLUSIONS: Compared with patients without ADHD, patients treated pharmacologically for ADHD experience similar weight loss and remission of obesity-related diseases without an increased risk for serious complications but report a lower health-related quality of life and have an increased risk of substance abuse and self-harm. This further emphasizes the need for close follow-up care for this group of individuals.

Palmitate impairs circadian transcriptomics in muscle cells through histone modification of enhancers.

Obesity and elevated circulating lipids may impair metabolism by disrupting the molecular circadian clock. We tested the hypothesis that lipid overload may interact with the circadian clock and alter the rhythmicity of gene expression through epigenomic mechanisms in skeletal muscle. Palmitate reprogrammed the circadian transcriptome in myotubes without altering the rhythmic mRNA expression of core clock genes. Genes with enhanced cycling in response to palmitate were associated with post-translational modification of histones. The cycling of histone 3 lysine 27 acetylation (H3K27ac), a marker of active gene enhancers, was modified by palmitate treatment. Chromatin immunoprecipitation and sequencing confirmed that palmitate exposure altered the cycling of DNA regions associated with H3K27ac. The overlap between mRNA and DNA regions associated with H3K27ac and the pharmacological inhibition of histone acetyltransferases revealed novel cycling genes associated with lipid exposure of primary human myotubes. Palmitate exposure disrupts transcriptomic rhythmicity and modifies enhancers through changes in histone H3K27 acetylation in a circadian manner. Thus, histone acetylation is responsive to lipid overload and may redirect the circadian chromatin landscape, leading to the reprogramming of circadian genes and pathways involved in lipid biosynthesis in skeletal muscle.

The effect of routine division of the greater omentum on small bowel obstruction after Roux-en-Y gastric bypass.

BACKGROUND: It remains unknown whether routine division of the greater omentum during laparoscopic Roux-en-Y gastric bypass (LRYGB) influences the risk for small bowel obstruction (SBO) after RYGB. OBJECTIVE: To evaluate the effect of omental division on SBO after LRYGB stratified by handling of the mesenteric defects. SETTING: Nationwide, registry-based. METHODS: In this registry-based cohort study, 40,517 patients who underwent LRYGB in Sweden within the period from January 1, 2007, to December 31, 2019, with data from the Scandinavian Obesity Surgery Registry (SOReg) were included. The study was based on combined data from the SOReg, the National Patient Register, the Swedish Prescribed Drugs Register, and the Total Population Registry. The main outcome was reoperation for SBO. RESULTS: During a follow-up period of 5.9 ± 2.6 years, the cumulative incidence of SBO was 11.2% in the nondivision group compared with 9.7% among patients with divided omentum (hazard ratio [HR] = .83, 95% confidence interval [CI]: .77-.89, P < .001). The association was seen in patients without mesenteric defects closure (HR = .69, 95% CI: .61-.78, P < .001) as well as patients with closed mesenteric defects (HR = .80, 95% CI: .74-.87, P < .001). CONCLUSION: Division of the greater omentum is associated with reduced risk for SBO after antecolic, antegastric LRYGB and should be considered as a complement to mesenteric defects closure to further reduce the risk for SBO after LRYGB.

Safety of bariatric surgery in patients with previous acute coronary events or heart failure: nationwide cohort study.

BACKGROUND: Metabolic (bariatric) surgery for patients with severe obesity and pre-existing heart disease has been reported to reduce the risk for cardiovascular events and mortality; however, concerns of short- and mid-term complications may limit the utility of metabolic surgery for these patients. METHOD: This was an observational, nationwide, matched study, including all adult patients operated with a primary gastric bypass or sleeve gastrectomy procedure in Sweden from January 2011 until October 2020. Patients with or without previous acute coronary syndrome or heart failure were matched 1:5 using propensity scores. The primary outcome was serious postoperative complications, and secondary outcomes were the occurrence of any short-term complications, mid-term complications, weight loss, and health-related quality of life estimates after surgery. RESULTS: Of patients who underwent metabolic surgery, 1165 patients with previous acute coronary syndrome or heart failure and 5825 without diagnosed heart disease were included in matched analyses. No difference was seen between the groups at risk for serious postoperative complications within 30 days of surgery (OR 1.33, 95 per cent c.i. 0.95 to 1.86, P = 0.094), whereas heart disease was associated with an increased risk for cardiovascular complications (incidence 1.1 per cent versus 0.2 per cent, P < 0.001). No differences in overall mid-term complications, weight loss, or improvement of health-related quality of life were seen. Pre-existing heart disease was associated with an increased risk for bowel obstruction and strictures (OR 1.89, 95 per cent c.i. 1.20 to 2.99, P = 0.006). CONCLUSION: Patients with severe obesity and heart disease undergoing metabolic surgery have an increased risk of postoperative cardiovascular complications compared with patients with severe obesity without heart disease. A careful preoperative cardiovascular work-up is needed but patients with severe obesity and heart disease should not be excluded from undergoing metabolic surgery.

Lipolysis defect in people with obesity who undergo metabolic surgery.

OBJECTIVE: Cross-sectional studies demonstrate that catecholamine stimulation of fat cell lipolysis is blunted in obesity. We investigated whether this defect persists after substantial weight loss has been induced by metabolic surgery, and whether it is related to the outcome. DESIGN/METHODS: Patients with obesity not able to successfully reduce body weight by conventional means (n = 126) were investigated before and 5 years after Roux-en-Y gastric bypass surgery (RYGB). They were compared with propensity-score matched subjects selected from a control group (n = 1017), and with the entire group after adjustment for age, sex, body mass index (BMI), fat cell volume and other clinical parameters. Catecholamine-stimulated lipolysis (glycerol release) was investigated in isolated fat cells using noradrenaline (natural hormone) or isoprenaline (synthetic beta-adrenoceptor agonist). RESULTS: Following RYGB, BMI was reduced from 39.9 (37.5-43.5) (median and interquartile range) to 29.5 (26.7-31.9) kg/m2 (p < 0.0001). The post-RYGB patients had about 50% lower lipolysis rates compared with the matched and total series of controls (p < 0.0005). Nordrenaline activation of lipolysis at baseline was associated with the RYGB effect; those with high lipolysis activation (upper tertile) lost 30%-45% more in body weight, BMI or fat mass than those with low (bottom tertile) initial lipolysis activation (p < 0.0007). CONCLUSION: Patients with obesity requiring metabolic surgery have impaired ability of catecholamines to stimulate lipolysis, which remains despite long-term normalization of body weight by RYGB. Furthermore, preoperative variations in the ability of catecholamines to activate lipolysis may predict the long-term reduction in body weight and fat mass.

Major cardiovascular events after metabolic surgery in patients with previous heart disease with or without type 2 diabetes: a nationwide cohort study.

BACKGROUND: While metabolic surgery is known to improve type 2 diabetes (T2D) as well as established heart disease separately, it is not known whether the outcome is influenced by T2D status in patients with established heart disease. OBJECTIVES: To evaluate the risks for major cardiovascular events (MACE) or mortality in patients with established heart disease with or without T2D. SETTING: Nationwide and registry-based (Sweden). METHODS: Patients with established heart disease operated with sleeve gastrectomy or Roux-en-Y gastric bypass in Sweden from 2007-2019 were matched 1:1 to normal population controls using 2-staged matching (exact matching on T2D, followed by optimal matching on propensity score for age, sex, dyslipidemia, chronic obstructive pulmonary disease, type of heart disease, T2D duration, county of residence, and level of education). The risk for MACE was evaluated separately depending on T2D status. RESULTS: In total, 1513 patients who underwent surgery and 1513 matched controls were included. Reduced risk for MACE and mortality were seen after metabolic surgery for patients with heart disease and T2D compared with controls (adjusted hazard ratio [HR] = .59, 95% confidence interval [CI]: .48-.72, P < .001, and adjusted HR = .52, 95% CI: .40-.67, P < .001, respectively), and for patients with heart disease alone compared with controls (adjusted HR = .73, 95% CI: .57-.94, P = .016, and adjusted HR = .63, 95% CI: .45-.89, P = .008, respectively). CONCLUSION: Metabolic surgery was associated with a reduced risk for MACE and mortality in patients with preexisting heart disease and T2D as well as in patients with heart disease without T2D. Patients with heart disease and T2D seem to experience the highest risk reduction.

Glutamine Regulates Skeletal Muscle Immunometabolism in Type 2 Diabetes.

Dysregulation of skeletal muscle metabolism influences whole-body insulin sensitivity and glucose homeostasis. We hypothesized that type 2 diabetes-associated alterations in the plasma metabolome directly contribute to skeletal muscle immunometabolism and the subsequent development of insulin resistance. To this end, we analyzed the plasma and skeletal muscle metabolite profile and identified glutamine as a key amino acid that correlates inversely with BMI and insulin resistance index (HOMA-IR) in men with normal glucose tolerance or type 2 diabetes. Using an in vitro model of human myotubes and an in vivo model of diet-induced obesity and insulin resistance in male mice, we provide evidence that glutamine levels directly influence the inflammatory response of skeletal muscle and regulate the expression of the adaptor protein GRB10, an inhibitor of insulin signaling. Moreover, we demonstrate that a systemic increase in glutamine levels in a mouse model of obesity improves insulin sensitivity and restores glucose homeostasis. We conclude that glutamine supplementation may represent a potential therapeutic strategy to prevent or delay the onset of insulin resistance in obesity by reducing inflammatory markers and promoting skeletal muscle insulin sensitivity.

Factors affecting relapse of type 2 diabetes after bariatric surgery in Sweden 2007-2015: a registry-based cohort study.

BACKGROUND: Although a large proportion of patients with type 2 diabetes (T2DM) who have undergone metabolic surgery experience initial remission some patients later suffer from relapse. While several factors associated with T2D remission are known, less is known about factors that may influence relapse. OBJECTIVES: To identify possible risk factors for T2D relapse in patients who initially experienced remission. SETTING: Nationwide, registry-based study. METHODS: We conducted a nationwide registry-based retrospective cohort study including all adult patients with T2D and body mass index ≥35 kg/m2 who received primary metabolic surgery with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in Sweden between 2007 and 2015. Patients who achieved complete diabetes remission 2 years after surgery was identified and analyzed. Main outcome measure was postoperative relapse of T2D, defined as reintroduction of diabetes medication. RESULTS: In total, 2090 patients in complete remission at 2 years after surgery were followed for a median of 5.9 years (interquartile range [IQR] 4.3-7.2 years) after surgery. The cumulative T2D relapse rate was 20.1%. Duration of diabetes (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.05-1.14; P < .001), preoperative glycosylated hemoglobin A1C (HbA1C) level (HR, 1.01; 95% CI, 1.00-1.02; P = .013), and preoperative insulin treatment (HR, 2.67; 95% CI, 1.84-3.90; P < .001) were associated with higher rates for relapse, while postoperative weight loss (HR, .93; 95% CI, .91-.96; P < .001), and male sex (HR, .65; 95% CI, .46-.91; P = .012) were associated with lower rates. CONCLUSION: Longer duration of T2D, higher preoperative HbA1C level, less postoperative weight loss, female sex, and insulin treatment prior to surgery are risk factors for T2D relapse after initial remission.

Remission, relapse, and risk of major cardiovascular events after metabolic surgery in persons with hypertension: A Swedish nationwide registry-based cohort study.

BACKGROUND: Several studies have shown that metabolic surgery is associated with remission of diabetes and hypertension. In terms of diabetes, factors such as duration, insulin use, weight loss, and age have been shown to contribute to the likelihood of remission. Such factors have not been determined for hypertension. The aim of this study was to evaluate factors associated with the remission and relapse of hypertension after metabolic surgery, as well as the risk for major adverse cardiovascular event (MACE) and mortality in patients with and without remission. METHODS AND FINDINGS: All adults who underwent metabolic surgery between January 2007 and June 2016 were identified in the nationwide Scandinavian Obesity Surgery Registry (SOReg). Through cross-linkage with the Swedish Prescribed Drug Register, Patient Register, and Statistics Sweden, individual data on prescriptions, inpatient and outpatient diagnoses, and mortality were retrieved. Of the 15,984 patients with pharmacologically treated hypertension, 6,286 (39.3%) were in remission at 2 years. High weight loss and male sex were associated with higher chance of remission, while duration, number of antihypertensive drugs, age, body mass index (BMI), cardiovascular disease, and dyslipidemia were associated with lower chance. After adjustment for age, sex, BMI, comorbidities, and education, the cumulative probabilities of MACEs (2.8% versus 5.7%, adjusted odds ratio (OR) 0.60, 95% confidence interval (CI) 0.47 to 0.77, p < 0.001) and all-cause mortality (4.0% versus 8.0%, adjusted OR 0.71, 95% CI 0.57 to 0.88, p = 0.002) were lower for patients being in remission at 2 years compared with patients not in remission, despite relapse of hypertension in 2,089 patients (cumulative probability 56.3%) during 10-year follow-up. The main limitations of the study were missing information on nonpharmacological treatment for hypertension and the observational study design. CONCLUSIONS: In this study, we observed an association between high postoperative weight loss and male sex with better chance of remission, while we observed a lower chance of remission depending on disease severity and presence of other metabolic comorbidities. Patients who achieved remission had a halved risk of MACE and death compared with those who did not. The results suggest that in patients with severe obesity and hypertension, metabolic surgery should not be delayed.