| 1. |
- Ahlin, Sofie, 1985, et al.
(author)
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Macrophage Gene Expression in Adipose Tissue is Associated with Insulin Sensitivity and Serum Lipid Levels Independent of Obesity.
- 2013
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In: Obesity (Silver Spring, Md.). - : Wiley. - 1930-739X .- 1930-7381. ; 21:12
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Journal article (peer-reviewed)abstract
- Objective: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. Design and Methods: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. Results: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group. Conclusion: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.
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| 2. |
- Andersson-Assarsson, Johanna C., 1974, et al.
(author)
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Evolution of age-related mutation-driven clonal haematopoiesis over 20 years is associated with metabolic dysfunction in obesity
- 2023
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In: Ebiomedicine. - 2352-3964. ; 92
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Journal article (peer-reviewed)abstract
- 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.
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| 3. |
- Carlsson, Lena M S, 1957, et al.
(author)
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Life expectancy after bariatric surgery or usual care in patients with or without baseline type 2 diabetes in Swedish Obese Subjects.
- 2023
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In: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
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Journal article (peer-reviewed)abstract
- 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.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.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)).Bariatric surgery is associated with similar reduction of overall and cardiovascular mortality and increased life expectancy regardless of baseline diabetes status.
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| 4. |
- Carlsson, Lena M S, 1957, et al.
(author)
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Long-term incidence of microvascular disease after bariatric surgery or usual care in patients with obesity, stratified by baseline glycaemic status: a post-hoc analysis of participants from the Swedish Obese Subjects study.
- 2017
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In: The lancet. Diabetes & endocrinology. - 2213-8595. ; 5:4, s. 271-279
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Journal article (peer-reviewed)abstract
- Bariatric surgery is associated with remission of diabetes and prevention of diabetic complications in patients with obesity and type 2 diabetes. Long-term effects of bariatric surgery on microvascular complications in patients with prediabetes are unknown. The aim of this study was to examine the effects of bariatric surgery on incidence of microvascular complications in patients with obesity stratified by baseline glycaemic status.Patients were recruited to the Swedish Obese Subjects (SOS) study between Sept 1, 1987, and Jan 31, 2001. Inclusion criteria were age 37-60 years and BMI of 34 kg/m(2) or greater in men and 38 kg/m(2) or greater in women. Exclusion criteria were identical in surgery and control groups and designed to exclude patients not suitable for surgery. The surgery group (n=2010) underwent gastric bypass (265 [13%]), gastric banding (376 [19%]), or vertical-banded gastroplasty (1369 [68%]). Participants in the control group (n=2037) received usual care. Bodyweight was measured and questionnaires were completed at baseline and at 0·5 years, 1 year, 2 years, 3 years, 4 years, 6 years, 8 years, 10 years, 15 years, and 20 years. Biochemical variables were measured at baseline and at 2 years, 10 years, and 15 years. We categorised participants into subgroups on the basis of baseline glycaemic status (normal [fasting blood glucose concentration <5·0 mmol/L], prediabetes [5·0-6·0 mmol/L], screen-detected diabetes [≥6·1 mmol/L at baseline visit without previous diagnosis], and established diabetes [diagnosis of diabetes before study inclusion]). We obtained data about first incidence of microvascular disease from nationwide registers and about diabetes incidence at study visits at 2 years, 10 years, and 15 years. We did the main analysis by intention to treat, and subgroup analyses after stratification by baseline glycaemic status and by diabetes status at the 15 year follow-up. The SOS study is registered with ClinicalTrials.gov, NCT01479452.4032 of the 4047 participants in the SOS study were included in this analysis. We excluded four patients with suspected type 1 diabetes, and 11 patients with unknown glycaemic status at baseline. At baseline, 2838 patients had normal blood glucose, 591 had prediabetes, 246 had screen-detected diabetes, and 357 had established diabetes. Median follow-up was 19 years (IQR 16-21). We identified 374 incident cases of microvascular disease in the control group and 224 in the surgery group (hazard ratio [HR] 0·56, 95% CI 0·48-0·66; p<0·0001). Interaction between baseline glycaemic status and effect of treatment on incidence of microvascular disease was significant (p=0·0003). Unadjusted HRs were lowest in the subgroup with prediabetes (0·18, 95% CI 0·11-0·30), followed by subgroups with screen-detected diabetes (0·39, 0·24-0·65), established diabetes (0·54, 0·40-0·72), and normoglycaemia (0·63, 0·48-0·81). Surgery was associated with reduced incidence of microvascular events in people with prediabetes regardless of whether they developed diabetes during follow-up.Bariatric surgery was associated with reduced risk of microvascular complications in all subgroups, but the greatest relative risk reduction was observed in patients with prediabetes at baseline. Our results suggest that prediabetes should be treated aggressively to prevent future microvascular events, and effective non-surgical treatments need to be developed for this purpose.US National Institutes of Health, Swedish Research Council, Sahlgrenska University Hospital Regional Agreement on Medical Education and Research, and Swedish Diabetes Foundation.
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| 5. |
- Carlsson, Lena M S, 1957, et al.
(author)
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Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
- 2019
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In: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
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Journal article (peer-reviewed)abstract
- Obesity increases risk of falling, but the effect of bariatric surgery on fall-related injuries is unknown. The aim of this study was therefore to study the association between bariatric surgery and long-term incidence of fall-related injuries in the prospective, controlled Swedish Obese Subjects study. At inclusion, body mass index was ≥ 34 kg/m2 in men and ≥38 kg/m2 in women. The surgery per-protocol group (n = 2007) underwent gastric bypass (n = 266), banding (n = 376), or vertical banded gastroplasty (n = 1365), and controls (n = 2040) received usual care. At the time of analysis (31 December 2013), median follow-up was 19 years (maximal 26 years). Fall-related injuries requiring hospital treatment were captured using data from the Swedish National Patient Register. During follow-up, there were 617 first-time fall-related injuries in the surgery group and 513 in the control group (adjusted hazard ratio 1.21, 95% CI, 1.07-1.36; P = 0.002). The incidence differed between treatment groups (P < 0.001, log-rank test) and was higher after gastric bypass than after usual care, banding and vertical banded gastroplasty (adjusted hazard ratio 0.50-0.52, P < 0.001 for all three comparisons). In conclusion, gastric bypass surgery was associated with increased risk of serious fall-related injury requiring hospital treatment.
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| 6. |
- Jacobson, Peter, 1962, et al.
(author)
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9p21.3 Coronary Artery Disease Locus Identifies Patients With Treatment Benefit From Bariatric Surgery in the Nonrandomized Prospective Controlled Swedish Obese Subjects Study.
- 2020
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In: Circulation. Genomic and precision medicine. - 2574-8300. ; 13:5, s. 460-465
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Journal article (peer-reviewed)abstract
- Sequence variation at chromosome 9p21.3 accounts for 20% of myocardial infarctions (MIs) in several populations. Whereas the risk conferred by the 9p21.3 locus appears to act independently of traditional risk factors, studies suggest that the association between 9p21.3 and MI is modified by glucose homeostasis and lifestyle. We examined if the 9p21.3 variant rs1333049, along with the previously identified predictor fasting insulin, modifies the preventive effect of bariatric surgery on MI incidence.rs1333049 was genotyped in 1852 patients treated by bariatric surgery and 1803 controls given usual care in the SOS study (Swedish Obese Subjects). MI incidence was determined using national registers. Median follow-up was 21 years (interquartile range 18-24 years).Overall, 366 MIs occurred during follow-up. Among rs1333049 risk-allele carriers (CC+GC), the incidence of MI was reduced in the surgery group compared with the control group (hazard ratio=0.72 [95% CI, 0.57-0.92], P=0.008). By contrast, noncarriers (GG) showed no significant differences in MI incidence between the treatment groups (hazard ratio=1.28 [0.86-1.90], P=0.227; interaction between treatment and the risk-allele P=0.016). In addition, carriers with higher fasting insulin (above the median [17 mmol/L]) experienced significantly higher MI incidence than carriers with lower fasting insulin (hazard ratio=0.58 [0.42-0.78], P<0.001, interaction P=0.031).In the SOS cohort, patients with the chromosome 9p21.3 rs1333049 risk allele together with high fasting insulin levels benefitted from bariatric surgery in terms of reduced incidence of MI. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01479452.
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| 7. |
- Kristensson, Felipe M., et al.
(author)
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Effects of Bariatric Surgery in Early- and Adult-Onset Obesity in the Prospective Controlled Swedish Obese Subjects Study.
- 2020
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In: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:4, s. 860-866
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Journal article (peer-reviewed)abstract
- Bariatric surgery is an effective treatment for obesity, but it is unknown if outcomes differ between adults with early- versus adult-onset obesity. We investigated how obesity status at 20 years of age affects outcomes after bariatric surgery later in life.The Swedish Obese Subjects study is a prospective matched study performed at 25 surgical departments and 480 primary health care centers. Participants aged 37-60 years with BMI ≥34 kg/m2 (men) or ≥38 kg/m2 (women) were recruited between 1987 and 2001; 2,007 participants received bariatric surgery and 2,040 usual care. Self-reported body weight at 20 years of age was used to stratify patients into subgroups with normal BMI (<25 kg/m2), overweight (BMI 25-29.9 kg/m2), or obesity (BMI ≥30 kg/m2). Body weight, energy intake, and type 2 diabetes status were examined over 10 years, and incidence of cardiovascular and microvascular disease was determined over up to 26 years using data from health registers.There were small but statistically significant differences in reduction of body weight among the subgroups after bariatric surgery (interaction P = 0.032), with the largest reductions among those with obesity aged 20 years. Bariatric surgery increased type 2 diabetes remission (odds ratios 4.51, 4.90, and 5.58 in subgroups with normal BMI, overweight, or obesity at 20 years of age, respectively; interaction P = 0.951), reduced type 2 diabetes incidence (odds ratios 0.15, 0.13, and 0.15, respectively; interaction P = 0.972), and reduced microvascular complications independent of obesity status at 20 years of age (interaction P = 0.650). The association between bariatric surgery and cardiovascular disease was similar in the subgroups (interaction P = 0.674). Surgical complications were similar in the subgroups.The treatment benefits of bariatric surgery in adults are similar regardless of obesity status at 20 years of age.
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| 8. |
- Lena, Carlsson, et al.
(author)
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Life Expectancy after Bariatric Surgery in the Swedish Obese Subjects Study.
- 2020
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In: The New England journal of medicine. - 1533-4406. ; 383:16, s. 1535-1543
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Journal article (peer-reviewed)abstract
- Obesity shortens life expectancy. Bariatric surgery is known to reduce the long-term relative risk of death, but its effect on life expectancy is unclear.We used the Gompertz proportional hazards regression model to compare mortality and life expectancy among patients treated with either bariatric surgery (surgery group) or usual obesity care (control group) in the prospective, controlled Swedish Obese Subjects (SOS) study and participants in the SOS reference study (reference cohort), a random sample from the general population.In total, 2007 and 2040 patients were included in the surgery group and the control group, respectively, and 1135 participants were included in the reference cohort. At the time of the analysis (December 31, 2018), the median duration of follow-up for mortality was 24 years (interquartile range, 22 to 27) in the surgery group and 22 years (interquartile range, 21 to 27) in the control group; data on mortality were available for 99.9% of patients in the study. In the SOS reference cohort, the median duration of follow-up was 20 years (interquartile range, 19 to 21), and data on mortality were available for 100% of participants. In total, 457 patients (22.8%) in the surgery group and 539 patients (26.4%) in the control group died (hazard ratio, 0.77; 95% confidence interval [CI], 0.68 to 0.87; P<0.001). The corresponding hazard ratio was 0.70 (95% CI, 0.57 to 0.85) for death from cardiovascular disease and 0.77 (95% CI, 0.61 to 0.96) for death from cancer. The adjusted median life expectancy in the surgery group was 3.0 years (95% CI, 1.8 to 4.2) longer than in the control group but 5.5 years shorter than in the general population. The 90-day postoperative mortality was 0.2%, and 2.9% of the patients in the surgery group underwent repeat surgery.Among patients with obesity, bariatric surgery was associated with longer life expectancy than usual obesity care. Mortality remained higher in both groups than in the general population. (Funded by the Swedish Research Council and others; SOS ClinicalTrials.gov number, NCT01479452.).
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| 9. |
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| 10. |
- Ahlin, Sofie, 1985, et al.
(author)
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Fracture risk after three bariatric surgery procedures in Swedish obese subjects : up to 26 years follow-up of a controlled intervention study
- 2020
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:5, s. 546-557
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Journal article (peer-reviewed)abstract
- Background: Previous studies have reported an increased fracture risk after bariatric surgery. Objective: To investigate the association between different bariatric surgery procedures and fracture risk. Methods: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups. Results: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02–3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41–2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66–2.79; P < 0.001). Conclusions: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment.
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