Mortality in relation to diabetes remission in Swedish Obese Subjects -a prospective cohort study.

BACKGROUND: People with obesity and type 2 diabetes (T2D) have reduced life expectancy, partly explained by increased risk of cardiovascular diseases and cancer. Here, we examined whether 2-year diabetes remission after bariatric surgery or usual care is associated with long-term mortality. MATERIALS AND METHODS: This report includes 586 participants with obesity and concomitant T2D from the prospective Swedish Obese Subjects (SOS) cohort study; 338 underwent bariatric surgery and 248 received usual obesity care. At inclusion, age was 37-60 years and BMI ≥34 kg/m2 in men and ≥38 kg/m2 in women. Median follow-up was 26.2 years (interquartile range 22.7-28.7). Diabetes status was determined using self-reported data on diabetes medication and in-study measures of blood glucose and HbA1c. The study was cross-linked to Swedish national registers for data on morbidity, death, and emigration. RESULTS: Overall, 284 participants, 71.9% of surgery and 16.5% of usual care patients, were in remission at the 2-year examination. During follow-up, mortality rates were 16.6 deaths per 1000 person-years (95% CI:13.7-20.1) in the remission subgroup and 26.0 deaths per 1000 person-years (95% CI:22.2-30.4) in the non-remission subgroup (adjusted hazard ratio (HRadj)=0.71, 95% CI:0.54-0.95, P=0.019). The adjusted median life expectancy in the remission subgroup was 2.5 years (95% CI:0.3-4.7) longer than in the non-remission subgroup. Specifically, remission was associated with decreased cardiovascular mortality (sub-HRadj=0.54, 95% CI:0.35-0.85, P=0.008), but no detectable association with cancer mortality was found (sub-HRadj=1.06, 95% CI:0.60-1.86), P=0.841). CONCLUSION: In this post-hoc analysis of data from the SOS study, patients who achieved short-term diabetes remission had increased life expectancy and decreased cardiovascular death over up to 32 years of follow-up. Future studies should confirm these findings.

Fifteen-year changes in health-related quality of life after bariatric surgery and non-surgical obesity treatment.

BACKGROUND: Evidence on the long-term (≥10 years) development of health-related quality of life (HRQoL) following bariatric surgery is still limited and mainly based on small-scale studies. This study aimed to investigate (1) 15-year changes in mental, physical, social, and obesity-related HRQoL after bariatric surgery and non-surgical obesity treatment; and (2) whether sociodemographic factors and pre-operative health status are associated with 15-year HRQoL changes in the surgery group. METHODS: Participants were from the non-randomized, prospective, controlled Swedish Obese Subjects study. The surgery group (N = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls (N = 2040) received usual obesity care. Recruitment took place in 1987-2001 and measurements (including six HRQoL scales) were administered before treatment and after 0.5, 1, 2, 3, 4, 6, 8, 10 and 15 years. Multilevel mixed-effect regression models using all observations for estimation were conducted. RESULTS: Surgical patients experienced greater 15-year improvements in perceived health and overall mood, and greater reductions in depression, obesity-related problems, and social interaction limitations than controls (all p < 0.001, adjusted for baseline differences). Effect size (ES) was classified as large only for obesity-related problems (ES = 0.82). At the 15-year follow-up, surgical patients reported better perceived health (p < 0.001) and less obesity-related problems (p = 0.020) than controls. In the surgery group, patients with baseline diabetes had smaller 15-year reductions in social interaction limitations (p < 0.001) and depression (p = 0.049) compared to those without baseline diabetes. Although surgical patients with a history of psychiatric disorder reported lower HRQoL than those without such history over the 15-year follow-up, there were no significant differences in the long-term improvements between the two groups (p = 0.211-0.902). CONCLUSIONS: Over 15 years, surgical patients experienced more positive development of HRQoL compared to those receiving usual care. This difference was large for obesity-related problems, but otherwise the differences were small. Patients with pre-operative diabetes might be at increased risk for smaller long-term HRQoL improvements.

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.

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.

Development and validation of an interpretable machine learning-based calculator for predicting 5-year weight trajectories after bariatric surgery: a multinational retrospective cohort SOPHIA study.

BACKGROUND: Weight loss trajectories after bariatric surgery vary widely between individuals, and predicting weight loss before the operation remains challenging. We aimed to develop a model using machine learning to provide individual preoperative prediction of 5-year weight loss trajectories after surgery. METHODS: In this multinational retrospective observational study we enrolled adult participants (aged ≥18 years) from ten prospective cohorts (including ABOS [NCT01129297], BAREVAL [NCT02310178], the Swedish Obese Subjects study, and a large cohort from the Dutch Obesity Clinic [Nederlandse Obesitas Kliniek]) and two randomised trials (SleevePass [NCT00793143] and SM-BOSS [NCT00356213]) in Europe, the Americas, and Asia, with a 5 year follow-up after Roux-en-Y gastric bypass, sleeve gastrectomy, or gastric band. Patients with a previous history of bariatric surgery or large delays between scheduled and actual visits were excluded. The training cohort comprised patients from two centres in France (ABOS and BAREVAL). The primary outcome was BMI at 5 years. A model was developed using least absolute shrinkage and selection operator to select variables and the classification and regression trees algorithm to build interpretable regression trees. The performances of the model were assessed through the median absolute deviation (MAD) and root mean squared error (RMSE) of BMI. FINDINGS: 10 231 patients from 12 centres in ten countries were included in the analysis, corresponding to 30 602 patient-years. Among participants in all 12 cohorts, 7701 (75·3%) were female, 2530 (24·7%) were male. Among 434 baseline attributes available in the training cohort, seven variables were selected: height, weight, intervention type, age, diabetes status, diabetes duration, and smoking status. At 5 years, across external testing cohorts the overall mean MAD BMI was 2·8 kg/m2 (95% CI 2·6-3·0) and mean RMSE BMI was 4·7 kg/m2 (4·4-5·0), and the mean difference between predicted and observed BMI was -0·3 kg/m2 (SD 4·7). This model is incorporated in an easy to use and interpretable web-based prediction tool to help inform clinical decision before surgery. INTERPRETATION: We developed a machine learning-based model, which is internationally validated, for predicting individual 5-year weight loss trajectories after three common bariatric interventions. FUNDING: SOPHIA Innovative Medicines Initiative 2 Joint Undertaking, supported by the EU's Horizon 2020 research and innovation programme, the European Federation of Pharmaceutical Industries and Associations, Type 1 Diabetes Exchange, and the Juvenile Diabetes Research Foundation and Obesity Action Coalition; Métropole Européenne de Lille; Agence Nationale de la Recherche; Institut national de recherche en sciences et technologies du numérique through the Artificial Intelligence chair Apprenf; Université de Lille Nord Europe's I-SITE EXPAND as part of the Bandits For Health project; Laboratoire d'excellence European Genomic Institute for Diabetes; Soutien aux Travaux Interdisciplinaires, Multi-établissements et Exploratoires programme by Conseil Régional Hauts-de-France (volet partenarial phase 2, project PERSO-SURG).

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.

Socioeconomic Disparities and Mediators for Recurrent Atherosclerotic Cardiovascular Disease Events After a First Myocardial Infarction.

BACKGROUND: Low socioeconomic status is associated with worse secondary prevention use and prognosis after myocardial infarction (MI). Actions for health equity improvements warrant identification of risk mediators. Therefore, we assessed mediators of the association between socioeconomic status and first recurrent atherosclerotic cardiovascular disease event (rASCVD) after MI. METHODS: In this cohort study on 1-year survivors of first-ever MI with Swedish universal health coverage ages 18 to 76 years, individual-level data from SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and linked national registries was collected from 2006 through 2020. Exposure was socioeconomic status by disposable income quintile (principal proxy), educational level, and marital status. The primary outcome was rASCVD and secondary outcomes were cardiovascular and all-cause mortality. We initially assessed the incremental attenuation of hazard ratios with 95% CIs in sequential multivariable models adding groups of potential mediators (ie, previous risk factors, acute presentation and infarct severity, initial therapies, and secondary prevention). Thereafter, the proportion of excess rASCVD associated with a low income mediated through nonparticipation in cardiac rehabilitation, suboptimal statin management, a cardiometabolic risk profile, persistent smoking, and blood pressure above target after MI were calculated using causal mediation analysis. RESULTS: Among 68 775 participants (73.8% men), 7064 rASCVD occurred during a mean 5.7-year follow-up. Income, adjusted for age, sex, and calendar year, was associated with rASCVD (hazard ratio, 1.63 [95% CI, 1.51-1.76] in the lowest versus highest income quintile). Risk attenuated most by adjustment for previous risk factors and by adding secondary prevention variables for a final model (hazard ratio, 1.38 [95% CI, 1.26-1.51]) in the lowest versus highest income quintile. The proportions of the excess 15-year rASCVD risk in the lowest income quintile mediated through nonparticipation in cardiac rehabilitation, cardiometabolic risk profile, persistent smoking, and poor blood pressure control were 3.3% (95% CI 2.1-4.8), 3.9% (95% CI, 2.9-5.5), 15.2% (95% 9.1-25.7), and 1.0% (95% CI 0.6-1.5), respectively. Risk mediation through optimal statin management was negligible. CONCLUSIONS: Nonparticipation in cardiac rehabilitation, a cardiometabolic risk profile, and persistent smoking mediate income-dependent prognosis after MI. In the absence of randomized trials, this causal inference approach may guide decisions to improve health equity.

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.

Seeking lifestyle counselling at primary health care centres: a cross-sectional study in the Swedish population.

BACKGROUND: Millions of people follow an unhealthy lifestyle in terms of tobacco consumption, hazardous use of alcohol, poor eating habits, and insufficient physical activity. Healthy lifestyles can to a large extent prevent and/or delay progression of non-communicable diseases. Factors influencing persons health-seeking behaviour regarding unhealthy lifestyles are of importance for sustainable health-promotive and disease-preventive work in primary health care. Generally, lifestyle interventions within primary health care are seen as feasible, but rarely reach all members of the general population. Few studies have been conducted about the likelihood among the general population to voluntarily contact a primary health care centre for support regarding lifestyle changes. The present study therefore aimed to investigate the general population's likelihood of contacting a primary health care centre regarding their lifestyles, and factors associated with a lower such likelihood. METHODS: A probability sample of adults living in Sweden (n = 3 750) were invited to participate in a cross-sectional survey regarding how societal developments affect attitudes and behaviours of the adult Swedish population. Data were collected between September and December 2020. Participants completed a questionnaire about lifestyle changes, and the data were analysed using descriptive statistics, Chi-square test and logistic regression analysis. RESULTS: The response rate was 52.0% (n = 1 896). Few persons responded that they would be likely to contact a primary health care centre for support regarding their lifestyles. Factors predicting a lower likelihood of contacting primary health care included few yearly visits to a primary health care centre, male sex, and living in a rural area. CONCLUSIONS: Primary health care centres are not the first choice for lifestyle counselling for the majority of adults living in Sweden. We have identified factors predicting low likelihood of using the support available at these centres. In order to work with sustainable and visible health-promotive and disease-preventive strategies at primary health care centres, these settings need to find valid methods to involve and collaborate with the members of the general community, to meet the needs of a population struggling with unhealthy lifestyles.

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.

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.

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.

Association of Socioeconomic Status With Risk Factor Target Achievements and Use of Secondary Prevention After Myocardial Infarction.

Importance: Low socioeconomic status (SES) is associated with poor long-term prognosis after myocardial infarction (MI). Plausible underlying mechanisms have received limited study. Objective: To assess whether SES is associated with risk factor target achievements or with risk-modifying activities, including cardiac rehabilitation programs, monitoring, and drug therapies, during the first year after MI. Design, Setting, and Participants: This cohort study included a population-based consecutive sample of 30 191 one-year survivors of first-ever MI who were 18 to 76 years of age, resided in the general community in Sweden, were followed up until their routine 11- to 15-month revisit, and were registered in the national registry Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) from 2006 through 2013. Data analyses were performed from January to August 2020. Exposure: Individual-level SES by proxy disposable income quintile. Secondary exposures were educational level and marital status. Main Outcomes and Measures: Odds ratios (ORs) with 95% CIs for achieved risk factor targets at the 1-year revisit and for use of guideline-recommended secondary prevention activities. Results: The study comprised 30 191 participants (72.9% men) with a mean (SD) age of 63.0 (8.6) years. Overall, higher SES was associated with better target achievements and use of most secondary prevention. The highest (vs lowest) income quintile was associated with achieved smoking cessation (OR, 2.05; 95% CI, 1.78-2.35), target blood pressure levels (OR, 1.17; 95% CI, 1.07-1.27), and glycated hemoglobin levels (OR, 1.57; 95% CI, 1.19-2.06). The highest-income quintile was associated not only with participation in physical training programs (OR, 2.28; 95% CI, 2.11-2.46) and patient educational sessions (OR, 2.29; 95% CI, 2.12-2.47) in cardiac rehabilitation but also with more monitoring of lipid profiles (OR, 1.20; 95% CI, 1.08-1.33) and intensification of statin therapy (OR, 1.22; 95% CI, 1.11-1.35) during the first year after MI. One year after MI, the highest-income quintile was associated with persistent use of statins (OR, 1.26; 95% CI, 1.10-1.45), high-intensity statins (OR, 1.10; 95% CI, 1.00-1.21), and renin-angiotensin-aldosterone system inhibitors (OR, 1.27; 95% CI, 1.08-1.49). Conclusions and Relevance: Findings indicated that, in a publicly financed health care system, higher SES was associated with better achievement of most risk factor targets, programs aimed at lifestyle change, and evidence-based drug therapies after MI. Observed differences in secondary prevention activity may be a factor in higher long-term risk of recurrent disease among individuals with low SES.

Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance.

Elucidation of mechanisms that govern lipid storage, oxidative stress, and insulin resistance may lead to improved therapeutic options for type 2 diabetes and other obesity-related diseases. Here, we find that adipose expression of the small neutral amino acid transporter SLC7A10, also known as alanine-serine-cysteine transporter-1 (ASC-1), shows strong inverse correlates with visceral adiposity, insulin resistance, and adipocyte hypertrophy across multiple cohorts. Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. Conversely, SLC7A10 overexpression decreases ROS generation and increases mitochondrial respiratory capacity. RNA sequencing revealed consistent changes in gene expression between human adipocytes and zebrafish visceral adipose tissue following loss of SLC7A10, e.g., upregulation of SCD (lipid storage) and downregulation of CPT1A (lipid oxidation). Interestingly, ROS scavenger reduced lipid accumulation and attenuated the lipid-storing effect of SLC7A10 inhibition. These data uncover adipocyte SLC7A10 as a novel important regulator of adipocyte resilience to nutrient and oxidative stress, in part by enhancing glutathione levels and mitochondrial respiration, conducive to decreased ROS generation, lipid accumulation, adipocyte hypertrophy, insulin resistance, and type 2 diabetes.

Prediction of Suicide and Nonfatal Self-harm After Bariatric Surgery: A Risk Score Based on Sociodemographic Factors, Lifestyle Behavior, and Mental Health: A Nonrandomized Controlled Trial.

OBJECTIVE: To identify preoperative sociodemographic and health-related factors that predict higher risk of nonfatal self-harm and suicide after bariatric surgery. BACKGROUND: Evidence is emerging that bariatric surgery is related to an increased risk of suicide and self-harm, but knowledge on whether certain preoperative characteristics further enhance the excess risk is scarce. METHODS: The nonrandomized, prospective, controlled Swedish Obese Subjects study was linked to 2 Nationwide Swedish registers. The bariatric surgery group (N = 2007, per-protocol) underwent gastric bypass, banding or vertical banded gastroplasty, and matched controls (N = 2040) received usual care. Participants were recruited from 1987 to 2001, and information on the outcome (a death by suicide or nonfatal self-harm event) was retrieved until the end of 2016. Subhazard ratios (sub-HR) were calculated using competing risk regression analysis. RESULTS: The risk for self-harm/suicide was almost twice as high in surgical patients compared to control patients both before and after adjusting for various baseline factors [adjusted sub-HR = 1.98, 95% confidence interval (CI) = 1.34-2.93]. Male sex, previous healthcare visits for self-harm or mental disorders, psychiatric drug use, and sleep difficulties predicted higher risk of self-harm/suicide in the multivariate models conducted in the surgery group. Interaction tests further indicated that the excess risk for self-harm/suicide related to bariatric surgery was stronger in men (sub-HR = 3.31, 95% CI = 1.73-6.31) than in women (sub-HR = 1.54, 95% CI = 1.02-2.32) (P = 0.007 for adjusted interaction). A simple-to-use score was developed to identify those at highest risk of these events in the surgery group. CONCLUSIONS: Our findings suggest that male sex, psychiatric disorder history, and sleep difficulties are important predictors for nonfatal self-harm and suicide in postbariatric patients. High-risk patients who undergo surgery might require regular postoperative psychosocial monitoring to reduce the risk for future self-harm behaviors.

Association of Metabolic Surgery With Major Adverse Cardiovascular Outcomes in Patients With Previous Myocardial Infarction and Severe Obesity: A Nationwide Cohort Study.

BACKGROUND: The number of patients with myocardial infarction and severe obesity is increasing and there is a lack of evidence how these patients should be treated. The aim of this study was to investigate the association between metabolic surgery (Roux-en-Y gastric bypass and sleeve gastrectomy) and major adverse cardiovascular events in patients with previous myocardial infarction (MI) and severe obesity. METHODS: Of 566 patients with previous MI registered in the SWEDEHEART registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) undergoing metabolic surgery and registered in the nationwide Scandinavian Obesity Surgery Registry, 509 patients (Roux-en-Y gastric bypass n=465; sleeve gastrectomy n=44) could be matched 1:1 to a control with MI from SWEDEHEART, but no subsequent metabolic surgery regarding sex, age (±3 years), year of MI (±3 years), and body mass index (±3). The 2 groups were well matched, except for a lower proportion of reduced ejection fraction after MI (7% versus 12%), previous heart failure (10% versus 19%), atrial fibrillation (6% versus 10%), and chronic obstructive pulmonary disease (4% versus 7%) in patients undergoing metabolic surgery. RESULTS: The median (interquartile range) follow-up time was 4.6 (2.7-7.1) years. The 8-year cumulative probability of major adverse cardiovascular events was lower in patients undergoing metabolic surgery (18.7% [95% CI, 15.9-21.5%] versus 36.2% [33.2-39.3%], adjusted hazard ratio, 0.44 [95% CI, 0.32-0.61]). Patients undergoing metabolic surgery had also a lower risk of death (adjusted HR, 0.45 [95% CI, 0.29-0.70]; MI, 0.24 [0.14-0.41]) and new onset heart failure, but there were no significant differences regarding stroke (0.91 [0.38-2.20]) and new onset atrial fibrillation (0.56 [0.31-1.01]). CONCLUSIONS: In severely obese patients with previous MI, metabolic surgery is associated with a low risk for serious complications, lower risk of major adverse cardiovascular events, death, new MI, and new onset heart failure. These findings need to be confirmed in a randomized, controlled trial.