| 1. |
- Shulman, Alexander, 1978, et al.
(författare)
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Incidence of end-stage renal disease following bariatric surgery in the Swedish Obese Subjects Study.
- 2018
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Ingår i: International journal of obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 42, s. 964-973
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a major public health problem leading to co-morbidities such as diabetes, hypertension and kidney failure. Bariatric surgery results in pronounced and maintained weight loss and prevention of obesity-related diseases and their complications. Most studies of bariatric surgery on kidney disease show improvements after surgery. However, long-term studies analyzing hard end-points are lacking. Here we report on the long-term effects of bariatric surgery compared to usual obesity care on incidence of end-stage renal disease (ESRD) alone and in combination with chronic kidney disease stage 4 (CKD4/ESRD).4047 patients were included in the Swedish Obese Subjects (SOS) study. Inclusion criteria were age 37-60 years and BMI≥34 in men and BMI≥38 in women. Patients in the bariatric surgery group (N=2010) underwent banding (18%), vertical banded gastroplasty (69%), or gastric bypass (13%); controls (N=2037) received usual obesity care. In this analysis, patients were followed up for a median time of 18 years. The incidence of ESRD and CKD4 was obtained by crosschecking the SOS database with the Swedish National Patient Register.During follow-up, ESRD occurred in 13 patients in the surgery group and in 26 patients in the control group (adjusted hazard ratio (HR)=0.27; 95% CI 0.12-0.60; p=0.001). The number of CKD4/ESRD events was 23 in the surgery group and 39 in the control group (adjusted HR=0.33; 95% CI 0.18-0.62; p<0.001). In both analyses, bariatric surgery had a more favorable effect in patients with baseline serum insulin levels above median compared to those with lower insulin levels (interaction p=0.010). Treatment benefit of bariatric surgery was also greater in patients with macroalbuminuria at baseline compared to those without macroalbuminuria (interaction p<0.001).Our study showed for the first time that bariatric surgery is associated with a long-term protection against ESRD and CKD4/ESRD.
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| 2. |
- Anveden, Åsa, et al.
(författare)
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Long-term incidence of female-specific cancer after bariatric surgery or usual care in the Swedish Obese Subjects Study
- 2017
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Ingår i: Gynecologic Oncology. - : Elsevier BV. - 0090-8258. ; 145:2, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To examine the long-term effects of bariatric surgery on female-specific cancer in women with obesity. Methods. The prospective, matched Swedish Obese Subjects (SOS) study was designed to examine outcomes after bariatric surgery. This study includes 1420 women from the SOS cohort that underwent bariatric surgery and 1447 contemporaneously matched controls who received conventional obesity treatment. Age was 3760 years and BMI was >= 38 kg/m(2). Information on cancer events was obtained from the Swedish National Cancer Registry. Median follow-up time was 18.1 years (interquartile range 14.8-20.9 years, maximum 26 years). This study is registered with ClinicalTrials.gov, NCT01479452. Results. Bariatric surgery was associated with reduced risk of overall cancer (hazard ratio = 0.71; 95% CI 0.59-0.85; p < 0.001). About half of the observed cancers were female-specific, and the incidence of these were lower in the surgery group compared with the control group (hazard ratio = 0.68; 95% CI 0.52-0.88; p = 0.004). The surgical treatment benefit with respect to female-specific cancer was significantly associated with baseline serum insulin (interaction p value = 0.022), with greater relative treatment benefit in patients with medium or high insulin levels. Separate analyses of different types of female-specific cancers showed that bariatric surgery was associated with reduced risk of endometrial cancer (hazard ratio = 0.56: 95% CI 035-0.89; p = 0.014). Conclusions. In this long-term study, bariatric surgery was associated with reduced risk of female-specific cancer, especially in women with hyperinsulinemia at baseline.
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| 3. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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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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Ingår i: The lancet. Diabetes & endocrinology. - 2213-8595. ; 5:4, s. 271-279
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Carlsson, Lena M S, 1957, et al.
(författare)
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Long-term incidence of serious fall-related injuries after bariatric surgery in Swedish obese subjects.
- 2019
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Ingår i: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 43:4, s. 933-937
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Tidskriftsartikel (refereegranskat)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≥34kg/m2 in men and ≥38kg/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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| 5. |
- Eisfeldt, J., et al.
(författare)
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AMYCNE: Confident copy number assessment using whole genome sequencing data
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variations (CNVs) within the human genome have been linked to a diversity of inherited diseases and phenotypic traits. The currently used methodology to measure copy numbers has limited resolution and/or precision, especially for regions with more than 4 copies. Whole genome sequencing (WGS) offers an alternative data source to allow for the detection and characterization of the copy number across different genomic regions in a single experiment. A plethora of tools have been developed to utilize WGS data for CNV detection. None of these tools are designed specifically to accurately estimate copy numbers of complex regions in a small cohort or clinical setting. Herein, we present AMYCNE (automatic modeling functionality for copy number estimation), a CNV analysis tool using WGS data. AMYCNE is multifunctional and performs copy number estimation of complex regions, annotation of VCF files, and CNV detection on individual samples. The performance of AMYCNE was evaluated using AMY1A ddPCR measurements from 86 unrelated individuals. In addition, we validated the accuracy of AMYCNE copy number predictions on two additional genes (FCGR3A and FCGR3B) using datasets available through the 1000 genomes consortium. Finally, we simulated levels of mosaic loss and gain of chromosome X and used this dataset for benchmarking AMYCNE. The results show a high concordance between AMYCNE and ddPCR, validating the use of AMYCNE to measure tandem AMY1 repeats with high accuracy. This opens up new possibilities for the use of WGS for accurate copy number determination of other complex regions in the genome in small cohorts or single individuals. © 2018 Eisfeldt et al.
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| 6. |
- Glad, Camilla A M, 1981, et al.
(författare)
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Expression of GHR and Downstream Signaling Genes in Human Adipose Tissue-Relation to Obesity and Weight Change.
- 2019
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 104:5, s. 1459-1470
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Tidskriftsartikel (refereegranskat)abstract
- GH is a strong regulator of metabolism. In obesity, both GH secretion and adipose tissue GHR gene expression are decreased. More detailed information on the regulation of GHR, STAT3/5, and downstream-regulated genes in human adipose tissue during diet-induced weight loss and weight gain is lacking.The aim of the present study was to investigate the gene expression patterns of GHR and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway (JAK2, STAT3, STAT5A, and STAT5B) in human subcutaneous adipose tissue in relation to energy restriction and overfeeding.Tissue distribution was analyzed in a data set generated by RNA sequencing containing information on global expression in human tissues. Subcutaneous adipose tissue or adipocyte gene expression (measured by DNA microarrays) was investigated in the following settings: (i) individuals with obesity vs individuals with normal weight; (ii) energy restriction; and (iii) overfeeding.GHR expression was decreased in subjects with obesity compared with subjects with normal weight (P < 0.001). It was increased in response to energy restriction and decreased in response to overfeeding (P = 0.015 and P = 0.030, respectively). STAT3 expression was increased in subjects with obesity (P < 0.001). It was decreased during energy restriction and increased during overfeeding (P = 0.004 and P = 0.006, respectively). STAT3-regulated genes showed an overall view of overexpression in obesity.The results of the present study have shown that GHR, STAT3, and STAT3-regulated genes are dynamically, and reciprocally, regulated at the tissue level in response to energy restriction and overfeeding, suggesting that GH signaling is perturbed in obesity.
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| 7. |
- Glad, Camilla A M, 1981, et al.
(författare)
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Reduced DNA methylation and psychopathology following endogenous hypercortisolism- a genome-wide study
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with Cushing's Syndrome (CS) in remission were used as a model to test the hypothesis that long-standing excessive cortisol exposure induces changes in DNA methylation that are associated with persisting neuropsychological consequences. Genome-wide DNA methylation was assessed in 48 women with CS in long-term remission (cases) and 16 controls matched for age, gender and education. The Fatigue impact scale and the comprehensive psychopathological rating scale were used to evaluate fatigue, depression and anxiety. Cases had lower average global DNA methylation than controls (81.2% vs 82.7%; p = 0.002). Four hundred and sixty-one differentially methylated regions, containing 3,246 probes mapping to 337 genes were identified. After adjustment for age and smoking, 731 probes in 236 genes were associated with psychopathology (fatigue, depression and/or anxiety). Twenty-four gene ontology terms were associated with psychopathology; terms related to retinoic acid receptor signalling were the most common (adjusted p = 0.0007). One gene in particular, COL11A2, was associated with fatigue following a false discovery rate correction. Our findings indicate that hypomethylation of FKBP5 and retinoic acid receptor related genes serve a potential mechanistic explanation for long-lasting GC-induced psychopathology.
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| 8. |
- Hjorth, Stephan, 1953, et al.
(författare)
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Reoperations After Bariatric Surgery in 26 Years of Follow-up of the Swedish Obese Subjects Study.
- 2019
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Ingår i: JAMA surgery. - : American Medical Association (AMA). - 2168-6262 .- 2168-6254. ; 154:4, s. 319-326
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Tidskriftsartikel (refereegranskat)abstract
- Bariatric surgery is an established treatment for obesity, but knowledge on the long-term incidence of revisional surgery is scarce.To determine the incidence and type of revisional surgery after bariatric surgery in 26 years of follow-up of participants in the Swedish Obese Subjects (SOS) study.The SOS study is a prospective nonrandomized controlled study comparing bariatric surgery (banding, vertical banded gastroplasty [VBG], and gastric bypass [GBP]) with usual care. The bariatric surgeries in the SOS study were conducted at 25 public surgical departments in Sweden. Men with body mass index values of 34 or higher and women with body mass indexes of 38 or higher were recruited to the surgery group of the SOS study between September 1, 1987, and January 31, 2001, and follow-up continued until December 31, 2014. Data analysis occurred from November 2016 to April 2018.Banding, VBG, or GBP.Revisional surgeries, analyzed using data from questionnaires, hospital records, and the Swedish National Patient register through December 31, 2014.A total of 2010 participants underwent surgery. The age range was 37 to 60 years. A total of 376 participants underwent banding (18.7%), while 1365 had VBG (67.9%) and 266 had GBP (13.2%). During a median follow-up of 19 years, 559 participants (27.8%) underwent first-time revisional surgery, including 354 conversions to other bariatric procedures (17.6%), 114 corrective surgeries (5.6%), and 91 reversals to normal anatomy (4.5%). Revisional surgeries (conversions, corrective surgery, and reversals) were common after banding (153 of 376 [40.7%]) and VBG (386 of 1365 [28.3%]) but relatively rare after GBP (20 of 266 [7.5%]). Patients who had banding and VBG primarily underwent conversions to GBP or reversals. Incidence of reversals was 5 times higher after banding than after VBG (40.7% vs 7.5%; unadjusted hazard ratio, 5.19 [95% CI, 3.43-7.87]; P<.001). Corrective surgeries were equally common irrespective of the index surgery (72 of 1365 patients who had VBG [5.3%]; 23 of 376 patients who had banding [6.1%]; 19 of 266 patients who had GBP [7.1%]). Revisional surgery indications, including inadequate weight loss, band-associated complications (migration, stenosis, and slippage), staple-line disruptions, and postsurgical morbidity, varied depending on index surgery subgroup. Most corrections occurred within the first 10 years, whereas conversions and reversals occurred over the entire follow-up period.Corrective surgeries occur mainly within the first 10 years and with similar incidences across all 3 surgical subgroups, but indications varied. Conversions (mainly to GBP) and reversals occurred after many years and were most frequent after banding and VBG, reflecting a higher overall revisional surgery demand after these operations.
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| 9. |
- 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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| 10. |
- Pettersson, M., et al.
(författare)
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Copy Number Variants Are Enriched in Individuals With Early-Onset Obesity and Highlight Novel Pathogenic Pathways
- 2017
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 102:8, s. 3029-3039
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Tidskriftsartikel (refereegranskat)abstract
- Context: Only a few genetic causes for childhood obesity have been identified to date. Copy number variants (CNVs) are known to contribute to obesity, both syndromic (15q11.2 deletions, Prader-Willi syndrome) and nonsyndromic (16p11.2 deletions) obesity. Objective: To study the contribution of CNVs to early-onset obesity and evaluate the expression of candidate genes in subcutaneous adipose tissue. Design and Setting: A case-control study in a tertiary academic center. Participants: CNV analysis was performed on 90 subjects with early-onset obesity and 67 normalweight controls. Subcutaneous adipose tissue from body mass index-discordant siblings was used for the gene expression analyses. Main Outcome Measures: We used custom high-density array comparative genomic hybridization with exon resolution in 1989 genes, including all known obesity loci. The expression of candidate genes was assessed using microarray analysis of messenger RNA from subcutaneous adipose tissue. Results: We identified rare CNVs in 17 subjects (19%) with obesity and 2 controls (3%). In three cases (3%), the identified variant involved a known syndromic lesion (22q11.21 duplication, 1q21.1 deletion, and 16p11.2 deletion, respectively), although the others were not known. Seven CNVs in 10 families were inherited and segregated with obesity. Expression analysis of 37 candidate genes showed discordant expression for 10 genes (PCM1, EFEMP1, MAMLD1, ACP6, BAZ2B, SORBS1, KLF15, MACROD2, ATR, and MBD5). Conclusions: Rare CNVs contribute possibly pathogenic alleles to a substantial fraction of children with early-onset obesity. The involved genes might provide insights into pathogenic mechanisms and involved cellular pathways. These findings highlight the importance of CNV screening in children with early-onset obesity.
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| 11. |
- Rukh, Gull, et al.
(författare)
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Dietary starch intake modifies the relation between copy number variation in the salivary amylase gene and BMI
- 2017
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 106:1, s. 256-262
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies have shown conflicting associations between the salivary amylase gene (AMY1) copy number and obesity. Salivary amylase initiates starch digestion in the oral cavity; starch is a major source of energy in the diet. Objective: We investigated the association between AMY1 copy number and obesity traits, and the effect of the interaction between AMY1 copy number and starch intake on these obesity traits. Design: We first assessed the association between AMY1 copy number (genotyped by digital droplet polymerase chain reaction) and obesity traits in 4800 individuals without diabetes (mean age: 57 y; 60% female) from the Malmo "Diet and Cancer Cohort. Then we analyzed interactions between AMY1 copy number and energyadjusted starch intake (obtained by a modified diet history method) on body mass index (BMI) and body fat percentage. Results: AMY1 copy number was not associated with BMI (P = 0.80) or body fat percentage (P = 0.38). We observed a significant effect of the interaction between AMY1 copy number and starch intake on BMI (P-interaction = 0.007) and body fat percentage (P-interaction = 0.03). Upon stratification by dietary starch intake, BMI tended to decrease with increasing AMY1 copy numbers in the low-starch intake group (P = 0.07) and tended to increase with increasing AMY1 copy numbers in the high-starch intake group (P = 0.08). The lowest mean BMI was observed in the group of participants with a low AMY1 copy number and a high dietary intake of starch. Conclusions: Our findings suggest an effect of the interaction between starch intake and AMY1 copy number on obesity. Individuals with high starch intake but low genetic capacity to digest starch had the lowest BMI, potentially because larger amounts of undigested starch are transported through the gastrointestinal tract, contributing to fewer calories extracted from ingested starch.
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| 12. |
- Shebanits, Kateryna, et al.
(författare)
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Copy number of pancreatic polypeptide receptor gene NPY4R correlates with body mass index and waist circumference
- 2018
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Multiple genetic studies have linked copy number variation (CNV) in different genes to body mass index (BMI) and obesity. A CNV on chromosome 10q11.22 has been associated with body weight. This CNV region spans NPY4R, the gene encoding the pancreatic polypeptide receptor Y4, which has been described as a satiety-stimulating receptor. We have investigated CNV of the NPY4R gene and analysed its relationship to BMI, waist circumference and self-reported dietary intake from 558 individuals (216 men and 342 women) representing a wide BMI range. The copy number for NPY4R ranged from 2 to 8 copies (average 4.6 +/- 0.8). Rather than the expected negative correlation, we observed a positive correlation between NPY4R copy number and BMI as well as waist circumference (r = 0.267, p = 2.65x 10(-7) and r = 0.256, p = 8x10(-7), respectively). Each additional copy of NPY4R correlated with 2.6 kg/m(2) increase in BMI and 5.67 cm increase in waist circumference (p = 3.3x10(-7) and p = 1x10(-6), respectively) for women. For men, there was no statistically significant correlation between CNV and BMI. Our results suggest that NPY4R genetic variation influences body weight in women, but the exact role of this receptor appears to be more complex than previously proposed.
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| 13. |
- Taube, Magdalena, et al.
(författare)
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Evaluation of reference genes for gene expression studies in human brown adipose tissue.
- 2015
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Ingår i: Adipocyte. - : Informa UK Limited. - 2162-3945 .- 2162-397X. ; 4:4, s. 280-5
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Tidskriftsartikel (refereegranskat)abstract
- Human brown adipose tissue (BAT) has during the last 5 year been subjected to an increasing research interest, due to its putative function as a target for future obesity treatments. The most commonly used method for molecular studies of human BAT is the quantitative polymerase chain reaction (qPCR). This method requires normalization to a reference gene (genes with uniform expression under different experimental conditions, e.g. similar expression levels between human BAT and WAT), but so far no evaluation of reference genes for human BAT has been performed. Two different microarray datasets with samples containing human BAT were used to search for genes with low variability in expression levels. Seven genes (FAM96B, GNB1, GNB2, HUWE1, PSMB2, RING1 and TPT1) identified by microarray analysis, and 8 commonly used reference genes (18S, B2M, GAPDH, LRP10, PPIA, RPLP0, UBC, and YWHAZ) were selected and further analyzed by quantitative PCR in both BAT containing perirenal adipose tissue and subcutaneous adipose tissue. Results were analyzed using 2 different algorithms (Normfinder and geNorm). Most of the commonly used reference genes displayed acceptably low variability (geNorm M-values <0.5) in the samples analyzed, but the novel reference genes identified by microarray displayed an even lower variability (M-values <0.25). Our data suggests that PSMB2, GNB2 and GNB1 are suitable novel reference genes for qPCR analysis of human BAT and we recommend that they are included in future gene expression studies of human BAT.
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| 14. |
- Viljakainen, H., et al.
(författare)
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Low Copy Number of the AMY1 Locus Is Associated with Early-Onset Female Obesity in Finland
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Background The salivary alpha-amylase locus (AMY1) is located in a highly polymorphic multi allelic copy number variable chromosomal region. A recent report identified an association between AMY1 copy numbers and BMI in common obesity. The present study investigated the relationship between AMY1 copy number, BMI and serum amylase in childhood-onset obesity. Sixty-one subjects with a history of childhood-onset obesity (mean age 19.1 years, 54% males) and 71 matched controls (19.8 yrs, 45% males) were included. All anthropometric measures were greater in the obese; their mean BMI was 40 kg/m(2) (range 25-62 kg/m(2)) compared with 23 kg/m(2) in the controls (15-32 kg/m(2)). Mean AMY1 copy numbers did not differ between the obese and control subjects, but gender differences were observed; obese men showed the highest and obese women the lowest number of AMY1 copies (p=0.045). Further, only in affected females, AMY1 copy number correlated significantly with whole body fat percent (r=-0.512, p=0.013) and BMI (r=-0.416, p=0.025). Finally, a clear linear association between AMY1 copy number and serum salivary amylase was observed in all subgroups but again differences existed between obese males and females. In conclusion, our findings suggest that AMY1 copy number differences play a role in childhood-onset obesity but the effect differs between males and females. Further studies in larger cohorts are needed to confirm these observations.
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| 15. |
- Zenténius, Edit, et al.
(författare)
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Self-Reported Weight-Loss Methods and Weight Change: Ten-Year Analysis in the Swedish Obese Subjects Study Control Group
- 2018
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 26:7, s. 1137-1143
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe Swedish Obese Subjects (SOS) study was designed to compare outcomes in patients with obesity treated by bariatric surgery and a matched control group given usual care. The aim of this study was to analyze self-reported weight-loss methods and weight changes over 10 years in the SOS control group. MethodsSelf-reported weight-loss methods in the control group (n=2,037; 71% women; 48.76.3 years; BMI 40.14.7 kg/m(2)) were analyzed at baseline and after 0.5, 1, 2, 3, 4, 6, 8, and 10 years of follow-up and studied in relation to weight changes. ResultsThe average 10-year weight change was +2.1% (95% CI: 1.4%-2.8%). At every follow-up, 82.7% (95% CI: 81.3%-84.1%) of participants reported weight-loss attempts. At 10 years, 12.5% of the participants had10% weight loss and 22.3% had10% weight gain. Participants who lost or gained weight reported similar usage of weight-loss methods. ConclusionsOver 10 years, the majority of the participants of the SOS control group reported continuous efforts to lose weight. These results illustrate the constant struggle individuals with severe obesity are facing and that, on average, the results of long-term weight loss and weight maintenance were discouraging.
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