| 1. |
- Andersson-Assarsson, Johanna C., 1974, et al.
(författare)
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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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Ingår i: Ebiomedicine. - 2352-3964. ; 92
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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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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Ingår i: International journal of obesity (2005). - 1476-5497. ; 47, s. 931-8
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Jacobson, Peter, 1962, et al.
(författare)
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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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Ingår i: Circulation. Genomic and precision medicine. - 2574-8300. ; 13:5, s. 460-465
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Kristensson, Felipe M., et al.
(författare)
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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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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:4, s. 860-866
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Tidskriftsartikel (refereegranskat)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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| 6. |
- van Deuren, Rosanne, et al.
(författare)
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Expansion of mutation-driven haematopoietic clones is associated with insulin resistance and low HDL-cholesterol in individuals with obesity
- 2021
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Ingår i: bioRxiv. - : Cold Spring Harbor Laboratory.
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- AimsHaematopoietic clones caused by somatic mutations with ≥2% variant allele frequency (VAF), known as clonal haematopoiesis of indeterminate potential (CHIP), increase with age and have been linked to risk of haematological malignancies and cardiovascular disease. Recent observations suggest that smaller clones are also associated with adverse clinical outcomes. Our aims were to determine the prevalence of clonal haematopoiesis driven by clones of variable sizes, and to examine the development of clones over time in relation to age and metabolic dysregulation over up to 20 years in individuals with obesity.Methods and ResultsWe used an ultrasensitive single-molecule molecular inversion probe sequencing assay to identify clonal haematopoiesis driver mutations (CHDMs) in blood samples from individuals with obesity from the Swedish Obese Subjects study. In a single-timepoint dataset with samples from 1050 individuals, we identified 273 candidate CHDMs in 216 individuals, with VAF ranging from 0.01% to 31.15% and CHDM prevalence and clone sizes increasing with age. Longitudinal analysis over 20 years in CHDM-positive samples from 40 individuals showed that small clones can grow over time and become CHIP. VAF increased on average by 7% (range -4% to 27%) per year. Rate of clone growth was positively associated with insulin resistance (R=0.40, P=0.025) and low circulating levels of high-density lipoprotein-cholesterol (HDL-C) (R=-0.68, P=1.74E-05).ConclusionOur results show that haematopoietic clones can be detected and monitored before they become CHIP and indicate that insulin resistance and low HDL-C, well-established cardiovascular risk factors, are associated with clonal expansion in individuals with obesity.Translational perspectivesClonal haematopoiesis-driver mutations are somatic mutations in haematopoietic stem cells that lead to clones detectable in peripheral blood. Haematopoietic clones with a variant allele frequency (VAF) ≥2%, known as clonal haematopoiesis of indeterminate potential (CHIP), are recognized as an independent cardiovascular risk factor. Here, we show that smaller clones are prevalent, and also correlate with age. Our longitudinal observations in individuals with obesity over 20 years showed that more than half of all clone-positive individuals show growing clones and clones with VAF <2% can grow and become CHIP. Importantly, clone growth was accelerated in individuals with insulin resistance and low high-density lipoprotein-cholesterol (HDL-C).Translational outlook 1: Haematopoietic clones can be detected and monitored before they become CHIP.Translational outlook 2: The association between insulin resistance and low HDL-C with growth of haematopoietic clones opens the possibility that treatments improving metabolism, such as weight loss, may reduce growth of clones and thereby cardiovascular risk.One Sentence SummaryIn obesity, the growth rate of mutation-driven haematopoietic clones increased with insulin resistance and low HDL-C, both known risk factors for cardiovascular disease.
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| 7. |
- Ahlin, Sofie, 1985, et al.
(författare)
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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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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:5, s. 546-557
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Anveden, Åsa, et al.
(författare)
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Long-term incidence of gallstone disease after bariatric surgery: results from the nonrandomized controlled Swedish Obese Subjects study
- 2020
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289. ; 16:10, s. 1474-1482
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gallstone disease is a known short-term complication of bariatric surgery; little is known of the long-term incidence. Objectives: The aim of this study was to investigate the association between bariatric surgery and long-term incidence of gallstone disease. Settings: A total of 25 surgery departments and 480 primary healthcare centers in Sweden. Methods: The Swedish Obese Subjects study is a prospective, controlled study comparing the effects of bariatric surgery with usual care with a follow-up of 20 years, including 4047 individuals. The current report includes all participants without previous or concomitant cholecystectomy (n = 3597). Operative techniques used in the surgery group (n = 1755) were gastric bypass (n = 236), vertical banded gastroplasty (n = 1202), and gastric banding (n = 317). The control group (n = 1842) received customary treatment for obesity. Gallstone disease was a predefined secondary endpoint in the Swedish Obese Subjects study and the primary endpoint of this report. Data were obtained by cross-checking our study database with the Swedish National Patient Register of diagnosis and procedures. Results: In the surgery and control groups, respectively, there were 307 and 252 first-time events of symptomatic gallstone disease and 230 and 170 cholecystectomies (log-rank P <.001, both outcomes). Bariatric surgery was associated with an increased risk of symptomatic gallstone disease, with a more pronounced risk during the first years of follow-up (P =.002) and an increased risk for cholecystectomy but with no time-varying effect (P =.213). Conclusions: Bariatric surgery increases the risk for symptomatic gallstone disease and cholecystectomy, especially during the first years following treatment. © 2020 American Society for Bariatric Surgery
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| 9. |
- Jamaly, Shabbar, 1965, et al.
(författare)
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Heart failure development in obesity: underlying risk factors and mechanistic pathways.
- 2021
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Ingår i: ESC heart failure. - : Wiley. - 2055-5822. ; 8:1, s. 356-367
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Tidskriftsartikel (refereegranskat)abstract
- People with obesity are at risk for developing heart failure (HF), but little is known about the mechanistic pathways that link obesity with cardiac dysfunction.We included 2030 participants from the Swedish Obese Subjects study who received conventional obesity treatment. First-time detection of HF was obtained by cross-checking the study population with the Swedish National Patient Register and the Swedish Cause of Death Register. We also examined if atrial fibrillation and myocardial infarction as time-dependent variables could predict incident HF The mean age of the study cohort was 48.7years, and 28% were men. The mean body mass index at baseline was 40.1kg/m2 and remained stable during a median follow-up of 20.1years. First-time diagnosis of HF occurred in 266 of patients and was related to male sex, increasing age, greater waist-hip ratio, hypertension, higher cholesterol, diabetes mellitus, and elevated free thyroxine in univariable analysis. Estimated glomerular filtration rate was negatively related to HF risk. In multivariable analysis, atrial fibrillation, which is related to HF with preserved ejection fraction (HFpEF), and myocardial infarction, which is linked to HF with reduced ejection fraction (HFrEF), were strongly associated with incident HF with sub-hazard ratios 3.75 (95% confidence interval: 2.72-5.18, P<0.001) and 3.68 (95% confidence interval: 2.55-5.30, P<0.001), respectively.Both atrial fibrillation and myocardial infarction as time-dependent variables were independently and strongly related to incident HF in people with excess body fat, suggesting two main obesity-related mechanistic pathways leading to either HFpEF or HFrEF.
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| 10. |
- Johansson, K., et al.
(författare)
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Long-term risk of anaemia after bariatric surgery: results from the Swedish Obese Subjects study
- 2021
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 9:8, s. 515-524
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Tidskriftsartikel (refereegranskat)abstract
- 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/m(2) or more (for men) or 38 kg/m(2) 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 personyears, 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 longterm compliance to nutritional supplementation and monitoring to enable prevention and early detection of serious nutritional deficiencies after bariatric surgery. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
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