| 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. |
- Kristensson, Felipe M., et al.
(författare)
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Breast Cancer Risk After Bariatric Surgery and Influence of Insulin Levels: A Nonrandomized Controlled Trial
- 2024
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Ingår i: JAMA Surgery. - 2168-6254 .- 2168-6262.
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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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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| 5. |
- Kristensson, Felipe M., et al.
(författare)
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Long-term effects of bariatric surgery in patients with obesity and chromosome 16 p11.2 microdeletion
- 2017
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Ingår i: Surgery for Obesity and Related Diseases. - : Elsevier BV. - 1550-7289. ; 13:8, s. 1321-1326
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chromosome 16 p11.2 microdeletion is associated with early-onset obesity. Information is limited about the effect of bariatric surgery in patients with genetic obesity. Objective: To examine the effects of bariatric surgery in obese patients with chromosome 16 p11.2 microdeletion. Methods: The Swedish Obese Subjects study is a prospective study with 2010 participants receiving bariatric surgery. DNA was available for 1843 participants. Multiplex ligation-dependent probe amplification was used to identify 16 p11.2 microdeletion carriers. Follow-up time was 10 years. In carriers and noncarriers, follow-up rate was 86% and 82%, respectively, at 10 years. Results: Nine carriers of the chromosome 16 p11.2 microdeletion (9/1843, .49%) were found. At baseline, most risk factors were similar; however, carriers had higher body mass index (BMI), insulin levels, and systolic blood pressure compared to noncarriers. At the 1 -year examination, the percent excess BMI lost (%EBMIL) in carriers and noncarriers was 71.9 and 62.2, respectively; P = .031 (37.9 and 30.6 kg). This was followed by partial weight regain in both groups, and after 10 years %BBMIL was 25.5 and 41.5 (15.7 and 21.3 kg), respectively (P = .377). Changes in risk factors were similar in the carriers and noncarriers. Two carriers who had type 2 diabetes at baseline were both in remission at 2 -year follow-up but relapsed at 10 -year follow-up. Perceived health status was similar in carriers and noncarriers during follow-up (overall P = .198). Conclusions: Despite a small sample size, our results indicate that bariatric surgery is a treatment option for obese patients with chromosome 16 p11.2 microdeletion. (Surg Obes Relat Dis 2017;13:1321-1326.) (C) 2017 American Society for Metabolic and Bariatric Surgery. All rights reserved.
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| 6. |
- Sjöholm, Kajsa, 1971, et al.
(författare)
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Association of Bariatric Surgery With Cancer Incidence in Patients With Obesity and Diabetes: Long-Term Results From the Swedish Obese Subjects Study.
- 2022
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:2, s. 444-450
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Tidskriftsartikel (refereegranskat)abstract
- 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.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).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).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.
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| 8. |
- 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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