Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels: A Nonrandomized Controlled Trial.

Importance: Obesity and insulin are risk factors for breast cancer, and retrospective studies suggest bariatric surgery reduces breast cancer risk in women. However, long-term prospective data on breast cancer risk after bariatric surgery and the role of baseline insulin levels are lacking. Objective: To examine if bariatric surgery is associated with breast cancer incidence in women and if treatment benefit is modified by baseline insulin levels. Design, Setting, and Participants: The Swedish Obese Subjects (SOS) study was a nonrandomized intervention trial designed to investigate the long-term effects of bariatric surgery on obesity-related mortality and morbidity. Study recruitment took place between 1987 and 2001, and median (IQR) follow-up time was 23.9 years (20.1-27.1) years. The study was conducted at 25 public surgical departments and 480 primary health care centers in Sweden and included 2867 women aged 37 to 60 years and with body mass index 38 or greater (calculated as weight in kilograms divided by height in meters squared). Intervention: In the surgery group (n = 1420), 260 women underwent gastric banding, 970 vertical banded gastroplasty, and 190 gastric bypass. The remaining contemporaneously matched control individuals (n = 1447) received usual obesity care. Main Outcome and Measures: Breast cancer, the main outcome of this secondary report, was not a predefined outcome in the SOS study. Breast cancer events were identified in the Swedish National Cancer Registry. Results: The study population comprised 2867 women with a mean (SD) age of 48.0 (6.2) years. During follow-up, there were 154 breast cancer events, 66 in the surgery group and 88 in the usual care group, and a decreased risk of breast cancer was observed in the bariatric surgery group (hazard ratio [HR], 0.68; 95% CI, 0.49-0.94; P = .019; adjusted HR, 0.72; 95% CI, 0.52-1.01; P = .06). The surgical treatment benefit on breast cancer risk was greater in women with baseline insulin levels above the median 15.8 µIU/L (HR, 0.48; 95% CI, 0.31-0.74; P = .001; adjusted HR, 0.55; 95% CI, 0.35-0.86; P = .008) compared to those below (HR, 0.95; 95% CI, 0.59-1.53; P = .84; adjusted HR, 1.01; 95% CI, 0.61-1.66; P = .97; interaction P = .02). Conclusions and Relevance: This prospective clinical trial indicated a reduced risk of breast cancer after bariatric surgery in women with obesity. The surgical treatment benefit was predominantly seen in women with hyperinsulinemia. Trial Registration: ClinicalTrials.gov Identifier: NCT01479452.

Cognitive functioning in adolescents with severe obesity undergoing bariatric surgery or intensive non-surgical treatment in Sweden (AMOS2): a multicentre, open-label, randomised controlled trial.

Background: Severe obesity during childhood is associated with cognitive deficits. Studies in adults have suggested improvements in executive functioning and memory after bariatric surgery. Our aim was to explore changes in cognitive function in adolescents over two years after bariatric surgery or intensive non-surgical treatment. Methods: The Adolescent Morbid Obesity Surgery 2 (AMOS2) is a multicentre, open-label, randomised controlled trial in which adolescents (aged 13-16 years) with severe obesity (defined as body mass index (BMI) ≥35 kg/m2) at three specialised obesity centres in Sweden, were randomly assigned to receive bariatric surgery or intensive non-surgical treatment. Herein we report the results of the prespecified exploratory endpoint of change in cognitive functioning. Inclusion in AMOS2 required Tanner pubertal stage ≥3, previous participation in lifestyle obesity treatment for at least one year, and passed assessment form a paediatrician and a paediatric psychologist. Adolescents with severe intellectual disability or other severe, pervasive developmental disorder were excluded. Participants underwent baseline assessment of general intellectual ability, executive functioning, and memory before randomisation. Tests were administrated by clinical psychologists and repeated at one- and two-year follow-up timepoints. Differences in means between groups during follow-up are provided with confidence intervals. The trial is registered at ClinicalTrials.gov, NCT02378259. Findings: Between October 28 2015 and June 7 2017, 46 adolescents (74% girls), with a mean age of 15.8 (±0.92) years and a mean BMI of 42.8 (±5.4) kg/m2, were included and randomised (23 to bariatric surgery and 23 to intensive non-surgical treatment). At baseline 23/46 (50%) of the adolescents had general intellectual functioning classified as borderline or below. For 15/18 (83%) aspects of cognitive functioning, no significant differences in change over two years were identified between groups; Immediate (average difference during follow-up 1.0 [95% CI: -2.6 to 4.6]) and Delayed (0.5 [95% CI: -0.6 to 1.6]) Verbal Recall, Category Fluency (1.1 [95% CI: -1.6 to 3.8]) and Switching (1.5 [95% CI: -0.0 to 2.9]), Number (-6.0 [95% CI: -12.3 to 0.3]) and Letter (0.1 [95% CI: -5.2 to 5.3]) Sequencing, Number-Letter Switching (-10.3 [95% CI: -26.4 to 5.8]), Motor Speed (-8.3 [95% CI: -17.5 to 0.9]), Colour Naming (-1.9 [95% CI: -4.2 to 0.3]), Inhibition (-3.6 [95% CI: -9.6 to 2.5]), Inhibition Switching (-6.7 [95% CI: -15.3 to 1.9]), Mazes (-0.5 [95% CI: -4.9 to 3.9]), Digit Span Forward (0.1 [95% CI: -0.6 to 0.9 ]) and Backward (0.6 [95% CI: -0.4 to 1.6 ]), and Estimated IQ (0.4 [95% CI: -3.9 to 4.8]; all p > 0.05). Three sub-tests assessing fundamental cognitive skills improved more over two years in operated adolescents than in intensive non-surgical treatment; Letter Fluency (average difference during follow-up 3.8 [95% CI: 0.1-7.5]; p = 0.046), Visual Scanning (-6.5 [95% CI: -11.6 to -1.5]; p = 0.011), and Word Reading (-1.9 [95% CI: -3.3 to -0.4]; p = 0.011). Interpretation: In contrast to non-randomised studies in adults, we could not demonstrate an association of bariatric surgery and its accompanying significant weight loss with overall greater improvement in executive functions and memory in adolescents over two years compared with a non-surgical group without weight loss. However, lack of statistical power is a potential limitation. The clinical relevance of greater improvements in basic cognitive skills needs to be explored. Funding: Sweden's innovation agency (VINNOVA), Swedish Research Council, Joanna Cocozza foundation for paediatric research, The Skane University Hospital Psychology Research and Development Grant, Tore Nilsson's Foundation, SUS Foundations and Donations, and Mary von Sydow's Foundation.

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.

Perceived Body Size in Relation to 10-Year Weight Change in the Swedish Obese Subjects Intervention Study.

INTRODUCTION: Body size underestimation in patients with obesity may be associated with long-term weight increase. In the current report, we analyse changes in body size perception in patients with obesity undergoing either bariatric surgery or usual obesity care, and in subgroups of patients who gain weight or maintain their body weight over 10 years. MATERIALS AND METHODS: A total of 2,504 patients with obesity from the prospective, controlled Swedish Obese Subjects (SOS) intervention study were included in this report, 1,370 patients underwent bariatric surgery and 1,134 patients were usual care controls. Weight was measured and body size was self-estimated using the Stunkard's figure rating scale at baseline and after 0.5, 1, 2, 3, 4, 6, 8 and 10 years of follow-up. A body perception index (BPI) was calculated as estimated/measured BMI. Weight (re)gain was defined as ≥10% increase between 1 and 10 years of follow-up. RESULTS: Body size was underestimated by 12% in the surgery and 14% in the control group (i.e., >5 BMI units) at baseline and underestimation largely persisted over 10 years in both intervention groups. When stratified by long-term weight development, weight regainers from the surgery group underestimated their body size to a larger degree compared to weight maintainers (12 vs. 9%, p < 0.001) after 10 years. Likewise weight gainers in the control group also underestimated their body size to a larger degree (17% vs. 13%, p < 0.001). In both groups, the change in BPI was significantly different between weight regainers and maintainers during follow-up (time-BPI interactions both p < 0.001). CONCLUSION: Patients with obesity underestimate their body size and this underestimation remains long-term even after major weight loss induced by bariatric surgery. In patients with obesity who maintain their weight, regardless of treatment, underestimation of body size persists but body size perception is slightly more accurate compared to patients who gain or regain weight long-term.

Long-term incidence of haematological cancer after bariatric surgery or usual care in the Swedish Obese Subjects study: a prospective cohort study.

BACKGROUND: Bariatric surgery in people with obesity is associated with a reduced overall cancer risk. Retrospective studies indicate that bariatric surgery specifically might reduce the risk of haematological cancers, but there is an absence of data from long-term, prospective studies. We therefore studied the association between bariatric surgery and haematological cancer in the Swedish Obese Subjects study. METHODS: The prospective controlled Swedish Obese Subjects study was designed to compare overall mortality in people who underwent bariatric surgery (n=2007) and usual care (n=2040). Participants were recruited through campaigns in mass media and at 480 primary health-care centres all over Sweden. The inclusion criteria were an age of 37-60 years and a BMI of 34 kg/m2 or more in men and 38 kg/m2 or more in women before or at the time of the examination. Haematological cancer events, including malignant lymphoma, myeloma, myeloproliferative neoplasms, as well as acute and chronic leukaemias, were captured from the Swedish Cancer Registry. The main outcome of this study was haematological cancer incidence and mortality. This study is registered with ClinicalTrials.gov (NCT01479452) and is ongoing. FINDINGS: A total of 4047 individuals with obesity were enrolled between Sept 1, 1987, and Jan 31, 2001. Overall, 34 participants in the surgery group and 51 participants in the usual care control group were diagnosed with haematological cancer during follow-up (hazard ratio [HR] 0·60; 95% CI 0·39-0·92; p=0·020). Moreover, there were three deaths by haematological cancer in the surgery group and 13 deaths in the control group (0·22; 0·06-0·76; p=0·017). Surgery was also associated with a reduced incidence of lymphoma (0·45; 0·23-0·88; p=0·020). A significant difference in treatment effect between men and women was found; bariatric surgery was associated with reduced incidence of haematological cancer in women (0·44; 0·26-0·74; p=0·002), but not in men (1·35; 0·58-3·17; p=0·489; interaction p=0·031). INTERPRETATION: Bariatric surgery is associated with a reduced incidence of haematological cancer, specifically in women. Health-care providers and policy makers working in the field of cancer prevention should consider bariatric surgery a primary prevention resource for people with obesity. FUNDING: The Swedish Research Council, the Swedish State under the agreement between the Swedish Government and the county councils, the Avtal om Läkarutbildning och Forskning agreement, the Health & Medical Care Committee of the Region Västra Götaland, the Swedish Heart Lung Foundation, Gothenburg Medical Society, and the Adlerbert Research Foundation. TRANSLATION: For the Swedish translation of the abstract see Supplementary Material section.

Non-alcohol substance use disorder after bariatric surgery in the prospective, controlled Swedish Obese Subjects study.

OBJECTIVE: The goal of this study was to investigate whether bariatric surgery is associated with substance use disorder (SUD) with substances other than alcohol. METHODS: The prospective, controlled Swedish Obese Subjects study enrolled 2010 patients with obesity who underwent bariatric surgery (gastric bypass n = 265; vertical banded gastroplasty n = 1369; gastric banding n = 376) and 2037 matched control individuals receiving usual obesity care. Participants with SUD other than alcohol use disorder were identified using International Statistical Classification of Diseases (ICD) codes from the Swedish National Patient Register (covering treatment in hospital but not primary care). Those with a history of non-alcohol SUD were excluded. Median follow-up was 23.8 years. RESULTS: During follow-up, non-alcohol SUD incidence rates per 1000 person-years with 95% CI were 1.6 (0.8-3.1), 0.8 (0.5-1.2), 1.1 (0.5-2.2), and 0.6 (0.4-0.8) for gastric bypass, vertical banded gastroplasty, gastric banding, and control individuals, respectively. Only gastric bypass was associated with increased incidence of non-alcohol SUD (adjusted hazard ratio 2.54 [95% CI: 1.14-5.65], p = 0.022) compared with control participants. CONCLUSIONS: Gastric bypass surgery was associated with increased risk of non-alcohol SUD, and this should be considered in long-term postoperative care.

Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.

OBJECTIVES: To determine life expectancy and causes of death after bariatric surgery in relation to baseline type 2 diabetes (T2D) in the prospective, Swedish Obese Subjects study. METHODS: The study included 2010 patients with obesity who underwent bariatric surgery and 2037 matched controls, eligible for surgery. The surgery group underwent gastric bypass (n = 265), banding (n = 376), or vertical banded gastroplasty (n = 1369). The control group (n = 2037) received usual obesity care. Causes of death were obtained from the Swedish Cause of Death Register, case sheets and autopsy reports, in patients with baseline T2D (n = 392 surgery patients/n = 305 controls) or non-T2D (n = 1609 surgery patients/n = 1726 controls) during a median follow-up 26 years. RESULTS: In T2D and non-T2D subgroups, bariatric surgery was associated with increased life expectancy (2.1, 95% confidence interval (95% CI) 0.2-4.0; and 1.6, 0.5-2.7 years, respectively) and reduced overall mortality (adjusted hazard ratio (adjHR) = 0.77, 95% CI: 0.61-0.97; and 0.82, 0.72-0.94, respectively), and the treatment benefit was similar (interaction p = 0.615). Bariatric surgery was associated with reduced cardiovascular mortality in both subgroups (adjHR = 0.65, 95% CI: 0.46-0.91; and 0.70, 0.55-0.88, respectively (interaction p = 0.516)). CONCLUSIONS: Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.

Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity.

BACKGROUND: Haematopoietic clones caused by somatic mutations with ≥2% variant allele frequency (VAF) increase with age and are linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones (VAF<2%) are also associated with adverse outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes in individuals with obesity treated by usual care or bariatric surgery (a treatment that improves metabolic status), and to examine the expansion of clones in relation to age and metabolic dysregulation over up to 20 years. METHODS: Clonal haematopoiesis-driver mutations (CHDMs) were identified in blood samples from participants of the Swedish Obese Subjects intervention study. Using an ultrasensitive assay, we analysed single-timepoint samples from 1050 individuals treated by usual care and 841 individuals who had undergone bariatric surgery, and multiple-timepoint samples taken over 20 years from a subset (n = 40) of the individuals treated by usual care. FINDINGS: In this explorative study, prevalence of CHDMs was similar in the single-timepoint usual care and bariatric surgery groups (20.6% and 22.5%, respectively, P = 0.330), with VAF ranging from 0.01% to 31.15%. Clone sizes increased with age in individuals with obesity, but not in those who underwent bariatric surgery. In the multiple-timepoint analysis, VAF increased by on average 7% (range -4% to 24%) per year and rate of clone growth was negatively associated with HDL-cholesterol (R = -0.68, 1.74 E-04). INTERPRETATION: Low HDL-C was associated with growth of haematopoietic clones in individuals with obesity treated by usual care. FUNDING: The Swedish Research Council, The Swedish state under an agreement between the Swedish government and the county councils, the ALF (Avtal om Läkarutbildning och Forskning) agreement, The Swedish Heart-Lung Foundation, The Novo Nordisk Foundation, The European Research Council, The Netherlands Organisation for Scientific Research.

Metabolic and bariatric surgery versus intensive non-surgical treatment for adolescents with severe obesity (AMOS2): a multicentre, randomised, controlled trial in Sweden.

BACKGROUND: Severe obesity in adolescents has a profound impact on current and future health. Metabolic and bariatric surgery (MBS) is increasingly used in adolescents internationally. However, to our knowledge, there are no randomised trials examining the currently most used surgical techniques. Our aim was to evaluate changes in BMI and secondary health and safety outcomes after MBS. METHODS: The Adolescent Morbid Obesity Surgery 2 (AMOS2) study is a randomised, open-label, multicentre trial done at three university hospitals in Sweden (located in Stockholm, Gothenburg, and Malmö). Adolescents aged 13-16 years with a BMI of at least 35 kg/m2, who had attended treatment for obesity for at least 1 year, passed assessments from a paediatric psychologist and a paediatrician, and had a Tanner pubertal stage of at least 3, were randomly assigned (1:1) to MBS or intensive non-surgical treatment. Exclusion criteria included monogenic or syndromic obesity, major psychiatric illness, and regular self-induced vomiting. Computerised randomisation was stratified for sex and recruitment site. Allocation was concealed for both staff and participants until the end of the inclusion day, and then all participants were unmasked to treatment intervention. One group underwent MBS (primarily gastric bypass), while the other group received intensive non-surgical treatment starting with 8 weeks of low-calorie diet. The primary outcome was 2-year change in BMI, analysed as intention-to-treat. The trial is registered at ClinicalTrials.gov, NCT02378259. FINDINGS: 500 people were assessed for eligibility between Aug 27, 2014, and June 7, 2017. 450 participants were excluded (397 did not meet inclusion criteria, 39 declined to participate, and 14 were excluded for various other reasons). Of the 50 remaining participants, 25 (19 females and six males) were randomly assigned to receive MBS and 25 (18 females and seven males) were assigned to intensive non-surgical treatment. Three participants (6%; one in the MBS group and two in the intensive non-surgical treatment group) did not participate in the 2-year follow-up, and in total 47 (94%) participants were assessed for the primary endpoint. Mean age of participants was 15·8 years (SD 0·9) and mean BMI at baseline was 42·6 kg/m2 (SD 5·2). After 2 years, BMI change was -12·6 kg/m2 (-35·9 kg; n=24) among adolescents undergoing MBS (Roux-en-Y gastric bypass [n=23], sleeve gastrectomy [n=2]) and -0·2 kg/m2 (0·4 kg; [n=23]) among participants in the intensive non-surgical treatment group (mean difference -12·4 kg/m2 [95% CI -15·5 to -9·3]; p<0·0001). Five (20%) patients in the intensive non-surgical group crossed over to MBS during the second year. Adverse events (n=4) after MBS were mild but included one cholecystectomy. Regarding safety outcomes, surgical patients had a reduction in bone mineral density, while controls were unchanged after 2 years (z-score change mean difference -0·9 [95% CI -1·2 to -0·6]). There were no significant differences between the groups in vitamin and mineral levels, gastrointestinal symptoms (except less reflux in the surgical group), or in mental health at the 2-year follow-up. INTERPRETATION: MBS is an effective and well tolerated treatment for adolescents with severe obesity resulting in substantial weight loss and improvements in several aspects of metabolic health and physical quality of life over 2 years, and should be considered in adolescents with severe obesity. FUNDING: Sweden's Innovation Agency, Swedish Research Council Health.

Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery.

BACKGROUND: Obesity is associated with incident heart failure (HF), but the underlying mechanisms are unclear. METHODS: We performed a nested case-control study within the Swedish-Obese-Subjects study, by identifying 411 cases who developed HF and matched them with respect to age, sex, weight-loss-surgery and length of follow-up with 410 controls who did not develop HF. In analyses corrected for multiple testing, we studied 182 plasma proteins known to be related to cardiovascular disease to investigate whether they could add to the understanding of the processes underlying obesity-related HF. RESULTS: A total of 821 subjects were followed for 16 ± 6 years. Multivariable analysis adjusted for matching variables revealed that 32 proteins were significantly associated with HF. Twelve proteins were related to HF ≥ 80% of the time using a bootstrap resampling approach (false-discovery-rate [FDR] < 0.05): 11 were associated with increased HF-risk: TNFRSF10A*, ST6GAL1, PRCP, MMP12, TIMP1, CCL3, QPCT, ANG, C1QTNF1, SERPINA5 and GAL-9; and one was related to reduced HF-risk: LPL. An further 20 proteins were associated with onset of HF 50-80% of the time using bootstrap resampling (FDR < 0.05). A pathway analysis including all significant 32 proteins suggested that these biomarkers were related to inflammation, matrix remodeling, cardiometabolic hormones and hemostasis. Three proteins, C1QTNF1, FGF-21 and CST3, reflecting dyslipidemia and kidney disease, displayed a higher association with HF in patients who did not undergo weight-loss-surgery and maintained with obesity. CONCLUSION: Pathways associated with HF in obesity include inflammation, matrix remodeling, cardiometabolic hormones and hemostasis; three protein biomarkers predicting HF appeared to be obesity-specific.

Risk factors for major gastrointestinal bleeding in the general population in Finland.

BACKGROUND: Data on non-drug related risk-factors for gastrointestinal bleeding (GIB) in the general population are limited, especially for life-style factors, clinical measurements and laboratory parameters. AIM: To identify and investigate non-drug risk factors for major GIB in the general population of Finland. METHODS: We performed a retrospective cohort study using data from the FINRISK health examination surveys, which have been conducted every 5 years across Finland from 1987 to 2007. Participants were adults aged 25 years to 74 years, excluding those with a previous hospitalization for GIB. Follow-up from enrollment was performed through linkage to national electronic health registers and ended at an event of GIB that led to hospitalization/death, death due to any other cause, or after 10 years. Covariates included demographics, socioeconomic and lifestyle factors, clinical measurements, laboratory parameters and comorbidities. Variable selection was undertaken using Least Absolute Shrinkage and Selection Operator (LASSO) and factors associated with GIB were identified using Cox regression. RESULTS: Among 33,508 participants, 403 (1.2%) experienced GIB [256 men (63.5%); mean age, 56.0 years (standard deviation (SD) ± 12.1)] and 33105 who did not experience GIB [15768 men (47.6%); mean age, 46.8 (SD ± 13) years], within 10 years of follow-up. Factors associated with a significantly increased risk of GIB were baseline age [per 10-year increase; hazard ratio (HR) 1.62, 95% confidence interval (CI): 1.42-1.86], unemployment (HR: 1.70, 95%CI: 1.11-2.59), body mass index (BMI) (HR: 1.15, 95%CI: 1.01-1.32), gamma-glutamyl transferase (GGT) (HR: 1.05, 95%CI: 1.02-1.09), precursors of GIB (HR: 1.90, 95%CI: 1.37-2.63), cancer (HR: 1.47, 95%CI: 1.10-1.97), psychiatric disorders (HR: 1.32, 95%CI: 1.01-1.71), heart failure (HR: 1.46, 95%CI: 1.04-2.05), and liver disorders (HR: 3.20, 95%CI: 2.06-4.97). Factors associated with a significantly decreased risk of GIB were systolic blood pressure (SBP) (HR: 0.78, 95%CI: 0.64-0.96), 6-10 cups of coffee a day (HR: 0.67, 95%CI: 0.46-0.99), or > 10 cups (HR: 0.43, 95%CI: 0.23-0.81). CONCLUSION: Our study confirms established risk-factors for GIB and identifies potential risk-factors not previously reported such as unemployment, BMI, GGT, SBP and coffee consumption.

Association of Bariatric Surgery With Cancer Incidence in Patients With Obesity and Diabetes: Long-term Results From the Swedish Obese Subjects Study.

OBJECTIVE: Obesity and type 2 diabetes are associated with serious adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study. RESEARCH DESIGN AND METHODS: The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of whom underwent bariatric surgery and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years). RESULTS: During follow-up, the incidence rate for first-time cancer was 9.1 per 1,000 person-years (95% CI 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1,000 person-years (95% CI 11.2-17.7) in patients treated with usual obesity care (adjusted hazard ratio 0.63 [95% CI 0.44-0.89], P = 0.008). Moreover, surgery was associated with reduced cancer incidence in women (0.58 [0.38-0.90], P = 0.016), although the sex-treatment interaction was nonsignificant (P = 0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (0.40 [0.22-0.74], P = 0.003). CONCLUSIONS: These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes and that durable diabetes remission is associated with reduced cancer risk.

Long-term risk of anaemia after bariatric surgery: results from the Swedish Obese Subjects study.

BACKGROUND: Nutritional deficiencies, such as iron and vitamin B12 deficiencies, are potential adverse consequences of bariatric surgery. Long-term data on anaemia after bariatric surgery are largely lacking. We aimed to investigate the risk of anaemia, iron and vitamin B12 deficiency anaemia, and vitamin B12 deficiency over 20 years in individuals who had bariatric surgery or received usual obesity care. METHODS: The prospective, controlled Swedish Obese Subjects study recruited people with obesity via recruitment campaigns in the mass media and at primary health-care centres, and was done at 480 primary health-care centres and in 25 surgical departments in Sweden. Eligible participants were aged 37-60 years and had a BMI of either 34 kg/m2 or more (for men) or 38 kg/m2 or more (for women). Participants were excluded if they had undergone previous bariatric surgery or had contraindicating conditions. Two main groups were formed: those who chose bariatric surgery, the type of which was determined by the operating surgeon, and a contemporaneously matched control group, created by use of 18 matching variables, who received usual non-surgical obesity care that ranged from lifestyle advice to no treatment. Haemoglobin concentration was measured during examination visits at baseline and at 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years of follow-up. Anaemia was defined as a haemoglobin concentration of less than 120 g/L for women and 130 g/L for men. The primary, non-specified outcome was the incidence of anaemia, and was assessed in the as-treated population, which comprised only patients who received the actual treatment. The associations between treatment type and anaemia are expressed as unadjusted hazard ratios (HRs) and HRs adjusted for age, sex, BMI, menopausal status, education, diabetes, and hypertension, with 95% CIs. This study is registered in ClinicalTrials.gov, NCT01479452, and is closed to new participants, with follow-up ongoing. FINDINGS: Between Sept 1, 1987, and Jan 31, 2001, 6905 individuals were assessed for eligibility, of whom 5335 were eligible. Of these, we included 2007 patients who chose bariatric surgery (266 in the gastric bypass group, 1365 in the vertical-banded gastroplasty group, and 376 in the gastric banding group) and 2040 matched controls who received usual obesity care. During a maximum of 20 years and a median of 10 years (IQR 3-20) of follow-up, there were 133 anaemia events in the gastric bypass group, 359 in the vertical-banded gastroplasty group, 101 in the gastric banding group, and 261 in the control group. Compared with the control group (13 cases per 1000 person-years, 95% CI 11-14), the incidence of anaemia was higher in the gastric bypass group (64 cases per 1000 person-years, 53-74; HR 5·05, 95% CI 3·94-6·48; p<0·0001), the vertical-banded gastroplasty group (23 cases per 1000 person-years, 21-26; 2·67, 2·25-3·18; p<0·0001), and the gastric banding group (26 per 1000 person-years, 21-31; 2·76, 2·15-3·52; p<0·0001). These associations remained after adjustment. INTERPRETATION: Our findings highlight the increased risk of anaemia after bariatric surgery and the importance of long-term compliance to nutritional supplementation and monitoring to enable prevention and early detection of serious nutritional deficiencies after bariatric surgery. FUNDING: Swedish Research Council, the Swedish state under the agreement between the Swedish Government and the county councils, the Swedish Diabetes Foundation, the Swedish Heart-Lung Foundation, and the Novo Nordisk Foundation.

Effect of a Multidomain Lifestyle Intervention on Estimated Dementia Risk.

We investigated the effect of a multidomain lifestyle intervention on the risk of dementia estimated using the validated CAIDE risk score (post-hoc analysis). The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a 2-year randomized controlled trial among 1,260 at-risk older adults (60-77 years). Difference in the estimated mean change in CAIDE score at 2 years in the intervention compared to the control group was -0.16 (95 %CI -0.31 to 0.00) (p = 0.013), corresponding to a relative dementia risk reduction between 6.04-6.50%. This could be interpreted as a reflection of the prevention potential of the intervention.

Long-term incidence of hypoglycaemia-related events after bariatric surgery or usual care in the Swedish Obese Subjects study: A register-based analysis.

AIMS: To examine the incidence of hypoglycaemia-related events over a period of up to 31 years in patients treated with bariatric surgery in the prospective, controlled Swedish Obese Subjects (SOS) study. MATERIALS AND METHODS: The SOS study (n = 4047) is a prospective controlled intervention study. The present analysis included 1989 patients treated with bariatric surgery and 2027 control patients with obesity who received usual care. Diagnosed hypoglycaemia and events commonly attributed to hypoglycaemia (confusion, syncope, epilepsy and seizures), requiring hospital or specialist outpatient treatment, were identified by searching the National Patient Register. Analyses were stratified by baseline glycaemic status. Hazard ratios were adjusted for inclusion year, age, sex, smoking, glycated haemoglobin (HbA1c) level and body mass index at baseline. At the time of analysis (December 31, 2018), the median follow-up was 22 years. RESULTS: Compared with usual care, bariatric surgery was associated with increased incidence of hypoglycaemia-related events in patients without baseline diabetes (168 and 219 events, respectively; log-rank P = .011), with a more pronounced risk during the first years of follow-up (test of time-treatment interaction P = .010). Multivariate analyses in patients without baseline diabetes indicated that male sex (P < .001), older age (P = .001) and higher HbA1c levels (P = .006) were associated with hypoglycaemia-related events. No association was found between risk of hypoglycaemia-related events and bariatric surgery in patients with baseline diabetes. CONCLUSIONS: Bariatric surgery is associated with an increased incidence of hypoglycaemia-related events in patients without baseline diabetes, especially during the first years after treatment.

Long-term incidence of colorectal cancer after bariatric surgery or usual care in the Swedish Obese Subjects study.

Bariatric surgery in patients with obesity is generally considered to reduce cancer risk in patients with obesity. However, for colorectal cancer some studies report an increased risk with bariatric surgery, whereas others report a decreased risk. These conflicting results demonstrate the need of more long-term studies analyzing the effect of bariatric surgery on colorectal cancer risk. Therefore, data from the Swedish Obese Subjects (SOS) study, ClinicalTrials.gov identifier: NCT01479452, was used to examine the impact of bariatric surgery on long-term incidence of colorectal cancer. The SOS study includes 2007 patients who underwent bariatric surgery and 2040 contemporaneously matched controls who received conventional obesity treatment. Patients in the surgery group underwent gastric bypass (n = 266), banding (n = 376) or vertical banded gastroplasty (n = 1365). Information on colorectal cancer events was obtained from the Swedish National Cancer Registry. Median follow-up was 22.2 years (inter-quartile range 18.3-25.2). During follow up there were 58 colorectal cancer events in the surgery group and 67 colorectal cancer events in the matched control group with a hazard ratio (HR) of 0.79 (95% CI:0.55-1.12; p = 0.183). After adjusting for age, body mass index, alcohol intake, smoking status, and diabetes, the adjusted HR was 0.89 (95% CI:0.62-1.29; p = 0.551). When analyzing rectal cancer events separately- 19 events in the surgery group and 31 events in the control group-a decreased risk of rectal cancer with surgery was observed (HR = 0.56; 95% CI:0.32-0.99; p = 0.045, adjusted HR = 0.61 (95% CI:0.34-1.10; p = 0.099), while the risk of colon cancer was unchanged. To conclude- in this long-term, prospective study, bariatric surgery was not associated with altered colorectal cancer risk.