L Sjöström

University of Gothenburg, Goeteborg, Västra Götaland, Sweden

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Publications (264)1589.01 Total impact

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    ABSTRACT: Objective The longitudinal associations between a dietary pattern (DP) and cardiometabolic risk factors and cardiovascular disease (CVD) incidence were investigated in a cohort of adults with severe obesity.Methods The analysis included 2,037 individuals with severe obesity (>34 and >38 kg/m2 for men and women, respectively) from the Swedish Obese Subjects study repeatedly followed up for 10 years. Reduced rank regression was used to identify a DP characterized by dietary energy density, saturated fat intake, and fiber density. Mixed models examined relationships between repeated measures of DP z-scores and cardiometabolic risk factors. Cox proportional hazards models assessed relationships between DP scores and CVD incidence.ResultsAn energy-dense, high-saturated-fat, and low-fiber DP was derived. A one-unit increase in the DP z-score between follow-ups was associated with an increase in weight [β (SE)] (1.71 ± 0.10 kg), waist circumference (1.49 ± 0.07 cm), BMI (0.60 ± 0.34 kg/m2), serum cholesterol (0.06 ± 0.01 mmol/l), and serum insulin (1.22 ± 0.17 mmol/l; all P < 0.0001), as well as in serum triglycerides (0.05 ± 0.02 mmol/l; P < 0.05), systolic blood pressure (1.05 ± 0.27 mmHg; P < 0.001), and diastolic blood pressure (0.55 ± 0.16 mmHg; P < 0.05). No significant association was observed between repeated measures of the DP z-scores and CVD incidence (HR = 0.96; 95% CI = 0.83-1.12).Conclusions An energy-dense, high-saturated-fat, and low-fiber DP was longitudinally associated with increases in cardiometabolic risk factors in severe obesity but not with CVD incidence.
    Obesity 04/2015; DOI:10.1002/oby.20920 · 4.39 Impact Factor
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    ABSTRACT: There is a need for a better understanding of the factors that influence long-term weight outcomes after bariatric surgery. We examined whether pretreatment and posttreatment levels of cognitive restraint, disinhibition, and hunger and 1-y changes in these eating behaviors predict short- and long-term weight changes after surgical and conventional treatments of severe obesity. Participants were from an ongoing, matched (nonrandomized) prospective intervention trial of the Swedish Obese Subjects (SOS) study. The current analyses included 2010 obese subjects who underwent bariatric surgery and 1916 contemporaneously matched obese controls who received conventional treatment. Physical measurements (e.g., weight and height) and questionnaires (e.g., Three-Factor Eating Questionnaire) were completed before the intervention and 0.5, 1, 2, 3, 4, 6, 8, and 10 y after the start of the treatment. Structural equation modeling was used as the main analytic strategy. The surgery group lost more weight and reported greater decreases in disinhibition and hunger at 1- and 10-y follow-ups (all P < 0.001 in both sexes) than the control group did. Pretreatment eating behaviors were unrelated to subsequent weight changes in surgically treated patients. However, patients who had lower levels of 6-mo and 1-y disinhibition and hunger (β = 0.13-0.29, P < 0.01 in men; β = 0.11-0.28, P < 0.001 in women) and experienced larger 1-y decreases in these behaviors (β = 0.31-0.48, P < 0.001 in men; β = 0.24-0.51, P < 0.001 in women) lost more weight 2, 6, and 10 y after surgery. In control patients, larger 1-y increases in cognitive restraint predicted a greater 2-y weight loss in both sexes. A higher tendency to eat in response to various internal and external cues shortly after surgery predicted less-successful short- and long-term weight outcomes, making postoperative susceptibility for uncontrolled eating an important indicator of targeted interventions. This trial was registered at clinicaltrials.gov as NCT01479452. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 01/2015; 101(1):16-24. DOI:10.3945/ajcn.114.095182 · 6.92 Impact Factor
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    ABSTRACT: Background/Objectives:The prevalence of obesity, defined as body mass index (BMI) ⩾30 kg/m(2), differs between populations; however, there is a need for data on description on body composition in reference populations of different ages and from different countries. The objective of this study was to pool dual-energy X-ray absorptiometry (DXA) body composition reference data from population-based Swedish cohorts.Subjects/Methods:Four population-based cross-sectional cohort studies including 1424 adult Swedes were divided into five age groups (20-29, 30-39, 40-49, 50-61 and 75 years of age); BMI 24.6±3.9 kg/m(2) were pooled. Body composition was measured with DXA.Results:The difference in BMI from the youngest to the oldest age group was 3.2 and 4.3 kg/m(2) in men and women, respectively (P<0.001, both sexes), and fat mass (FM) was 9.9 and 9.1% higher in the oldest compared with the youngest men and women (P<0.001, both sexes). Fat-free mass (FFM) remained stable up to 60 years of age in men (P=0.83) and was lower at 75 years of age compared with the younger ages. In women, FFM was lower from age 60. From youngest to oldest age groups, height-adjusted FM differed from 4.6 to 7.8 kg/m(2) in men and from 6.8 to 10.8 kg/m(2) in women (P<0.001, both sexes).Conclusions:Our results provide reference data on body composition in Swedish populations. BMI and FM were higher among older age groups compared with the younger ones. FFM remained stable up to 60 years of age and was lower first among the 75 years of age.European Journal of Clinical Nutrition advance online publication, 17 December 2014; doi:10.1038/ejcn.2014.268.
    European Journal of Clinical Nutrition 12/2014; DOI:10.1038/ejcn.2014.268 · 2.95 Impact Factor
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    ABSTRACT: Objective: To test the hypothesis that the growth hormone (GH) receptor (GHR) d3/fl polymorphism influences anthropometry and body composition in the general population. Design and Setting: The Swedish Obese Subjects (SOS) reference study is a cross-sectional population-based study, randomly selected from a population registry. A sub-group of the population-based Malmö Diet and Cancer Study (MDC-CC) was used as a replication cohort. Methods: The SOS reference study comprises 1135 subjects (46.2% men), with an average age of 49.5 yrs. The MDC-CC includes 5451 successfully genotyped subjects (41.5% men), with an average age of 57.5 yrs. GHR d3/fl genotypes were determined using tagSNP rs6873545. Linear regression analyses were used to test for genotype - phenotype associations. Results: In the SOS reference study, subjects homozygous for the d3-GHR weighed approximately four kilos more (p=0.011), had larger waist-to-hip ratio (WHR, p=0.036), waist circumference (p=0.016) and more fat free mass estimated from total body potassium (TBK, p=0.026) than grouped fl/d3 and fl/fl subjects (d3-recessive genetic model). The association with WHR was replicated in the MDC-CC (p=0.002), but not those with other anthropometric traits. Conclusions: In this population-based study the GHR d3/fl polymorphism was found to be of functional relevance and associated with central adiposity, such that subjects homozygous for the d3-GHR showed an increased abdominal obesity.
    European Journal of Endocrinology 11/2014; DOI:10.1530/EJE-14-0723 · 3.69 Impact Factor
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    ABSTRACT: Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis may progress to fibrosis and may promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver due to reduced secretion of very low density lipoproteins. As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of nonalcoholic steatohepatitis. Liver damage was evaluated in 1201 patients who underwent liver biopsy for suspected nonalcoholic steatohepatitis; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1819 controls from the Swedish Obese Subjects cohort.Presence of the inherited TM6SF2 E167K variant was determined by Taqman assays. In the liver biopsy cohort, 188 subjects (13%) were carriers of the E167K variant. They had lower serum lipid levels than noncarriers (P<0.05), had more severe steatosis, necroinflammation, ballooning, and fibrosis (P<0.05), and were more likely to have nonalcoholic steatohepatitis (OR 1.84, 95% CI 1.23-2.79) and advanced fibrosis (OR 2.08, 95% CI 1.20-3.55), after adjustment for age, sex, body mass index, fasting hyperglycemia, and the I148M PNPLA3 risk variant. However, E167K carriers had lower risk of developing carotid plaques (OR 0.49, 95% CI 0.25-0.94). In the Swedish Obese Subjects cohort, E167K carriers had higher ALT and lower lipid levels (P<0.05), and a lower incidence of cardiovascular events (HR 0.61, 95% CI 0.39-0.95). Conclusions: Carriers of the TM6SF2 E167K variant are more susceptible to progressive nonalcoholic steatohepatitis, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export very low density lipoproteins is deleterious for the liver. (Hepatology 2014;)
    Hepatology 09/2014; DOI:10.1002/hep.27490 · 11.19 Impact Factor
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    ABSTRACT: IMPORTANCE Short-term studies show that bariatric surgery causes remission of diabetes. The long-term outcomes for remission and diabetes-related complications are not known. OBJECTIVES To determine the long-term diabetes remission rates and the cumulative incidence of microvascular and macrovascular diabetes complications after bariatric surgery. DESIGN, SETTING, AND PARTICIPANTS The Swedish Obese Subjects (SOS) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary health care centers in Sweden. Of patients recruited between September 1, 1987, and January 31, 2001, 260 of 2037 control patients and 343 of 2010 surgery patients had type 2 diabetes at baseline. For the current analysis, diabetes status was determined at SOS health examinations until May 22, 2013. Information on diabetes complications was obtained from national health registers until December 31, 2012. Participation rates at the 2-, 10-, and 15-year examinations were 81%, 58%, and 41% in the control group and 90%, 76%, and 47% in the surgery group. For diabetes assessment, the median follow-up time was 10 years (interquartile range [IQR], 2-15) and 10 years (IQR, 10-15) in the control and surgery groups, respectively. For diabetes complications, the median follow-up time was 17.6 years (IQR, 14.2-19.8) and 18.1 years (IQR, 15.2-21.1) in the control and surgery groups, respectively. INTERVENTIONS Adjustable or nonadjustable banding (n = 61), vertical banded gastroplasty (n = 227), or gastric bypass (n = 55) procedures were performed in the surgery group, and usual obesity and diabetes care was provided to the control group. MAIN OUTCOMES AND MEASURES Diabetes remission, relapse, and diabetes complications. Remission was defined as blood glucose <110 mg/dL and no diabetes medication. RESULTS The diabetes remission rate 2 years after surgery was 16.4% (95% CI, 11.7%-22.2%; 34/207) for control patients and 72.3% (95% CI, 66.9%-77.2%; 219/303) for bariatric surgery patients (odds ratio [OR], 13.3; 95% CI, 8.5-20.7; P < .001). At 15 years, the diabetes remission rates decreased to 6.5% (4/62) for control patients and to 30.4% (35/115) for bariatric surgery patients (OR, 6.3; 95% CI, 2.1-18.9; P < .001). With long-term follow-up, the cumulative incidence of microvascular complications was 41.8 per 1000 person-years (95% CI, 35.3-49.5) for control patients and 20.6 per 1000 person-years (95% CI, 17.0-24.9) in the surgery group (hazard ratio [HR], 0.44; 95% CI, 0.34-0.56; P < .001). Macrovascular complications were observed in 44.2 per 1000 person-years (95% CI, 37.5-52.1) in control patients and 31.7 per 1000 person-years (95% CI, 27.0-37.2) for the surgical group (HR, 0.68; 95% CI, 0.54-0.85; P = .001). CONCLUSIONS AND RELEVANCE In this very long-term follow-up observational study of obese patients with type 2 diabetes, bariatric surgery was associated with more frequent diabetes remission and fewer complications than usual care. These findings require confirmation in randomized trials. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01479452.
    JAMA The Journal of the American Medical Association 06/2014; 311(22):2297-2304. DOI:10.1001/jama.2014.5988 · 30.39 Impact Factor
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    ABSTRACT: Understanding how dietary intake changes over time is important for studies of diet and disease and may inform interventions to improve dietary intakes. We investigated how a dietary pattern (DP) tracked over 10-years in the Swedish Obese Subjects (SOS) study control group. Dietary intake was assessed at multiple time-points in 2037 severely obese individuals (BMI 41±4 kg/m2). Reduced rank regression was used to derive a dietary pattern using dietary energy density (kJ/g), saturated fat (%) and fibre density (mg/kJ) as response variables and score respondents at each follow-up. Tracking coefficients for the DP, its key foods and macronutrient response variables and corrected for time-dependent and time-independent covariates were calculated using generalised estimating equations to take into account all available data. The DP tracking coefficient was moderate for women (0.40; 95% CI: 0.38-0.42) and men (0.38; 95% CI: 0.35-0.41). Of the eleven foods key to this DP, fruit and vegetable intakes had the strongest tracking coefficient for both sexes. Fast food and candy had the lowest tracking coefficients for women and men respectively. Scores for an energy dense, high saturated fat, low fibre density DP appear moderately stable over a 10-year period in this severely obese population. Furthermore, some food groups appear more amenable to change while others, often the most healthful, appear more stable and may require intervention before adulthood.
    PLoS ONE 05/2014; 9(5):e97457. DOI:10.1371/journal.pone.0097457 · 3.53 Impact Factor
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    ABSTRACT: Background Obesity is associated with increased risk of chronic kidney disease and albuminuria is a predictor of renal impairment. Bariatric surgery reduces body weight in obese subjects, but it is not known whether surgery can prevent development of albuminuria. This study aims to determine the long-term effect of bariatric surgery on the incidence of albuminuria.SubjectsThe Swedish Obese Subjects study is a nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden. Between September 1, 1987 and January 31, 2001, 2010 participants who underwent bariatric surgery and 2037 controls were recruited. Inclusion criteria were age 37-60 years and BMI⩾34 in men and BMI⩾38 in women. In this analysis, we included 1498 patients in the surgery group and 1610 controls without albuminuria at baseline. Patients in the bariatric-surgery group underwent banding (18%), vertical banded gastroplasty (69%), or gastric bypass (13%); controls received usual obesity care. Date of analysis was January 1, 2011. Median follow up was 10 years, and the rates of follow up were 87%, 74% and 52% at 2, 10 and 15 years, respectively. The main outcome of this report is incidence of albuminuria (defined as urinary albumin excretion>30 mg/24 hours) over up to 15 years.ResultsDuring the follow-up, albuminuria developed in 246 participants in the control group and in 126 in the bariatric surgery group, corresponding to incidence rates of 20.4 and 9.4 per 1000 person-years, respectively (adjusted hazard ratio, 0.37; 95% confidence interval, 0.30 to 0.47; P<0.001). The expected number of surgeries needed to prevent the development of albuminuria in one patient at 10 years was 9.Conclusions Bariatric surgery is associated with reduced incidence of albuminuria compared to usual obesity care.International Journal of Obesity accepted article preview online, 06 May 2014; doi:10.1038/ijo.2014.72.
    International journal of obesity (2005) 05/2014; 39(1). DOI:10.1038/ijo.2014.72 · 5.39 Impact Factor
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    ABSTRACT: OBJECTIVE Adiponectin has been implicated in the pathogenesis of type 2 diabetes, but its role for incident diabetes, myocardial infarction, or stroke in obesity is unclear. The aim of this study was to analyze the associations between systemic levels of adiponectin and the aforementioned outcomes in a population with severe obesity at high risk of diabetes and cardiovascular events.RESEARCH DESIGN AND METHODS We measured serum concentrations of total adiponectin in 3,299 participants of the prospective controlled Swedish Obese Subjects (SOS) Study (bariatric surgery group, n = 1,570; control group given usual care, n = 1,729). Median follow-up periods ranged between 10 and 13 years for different outcomes.RESULTSIn models containing both baseline adiponectin and 2-year changes in adiponectin, high baseline adiponectin and 2-year increases in adiponectin were associated with decreased risk of diabetes and myocardial infarction among controls. In the surgery group, the 2-year weight loss was paralleled by substantial increase in circulating adiponectin (1,807-1,958 ng/mL per 10-kg weight loss). However, neither baseline adiponectin nor 2-year increases in adiponectin were associated with risk of diabetes or myocardial infarction in the fully adjusted models in the surgery group. No associations were found for stroke in either group.CONCLUSIONS Taken together, baseline adiponectin and 2-year changes were associated with incident diabetes and myocardial infarction in the control group but not in the surgery group. Baseline adiponectin did not predict treatment benefit of bariatric surgery.
    Diabetes care 02/2014; 37(5). DOI:10.2337/dc13-1362 · 8.57 Impact Factor
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    ABSTRACT: Obesity is known to be associated with carotid artery remodelling, but less is known about how body fat distribution, inflammation and weight loss may affect this relation. Ultrasonography, dual-energy X-ray absorptiometry and computed tomography were performed to evaluate carotid artery intima-media thickness (IMT), body composition and fat distribution, respectively. Participants were divided into three matched study groups (n = 44 per group): obese patients with sustained weight loss 10 years after bariatric surgery [surgery group, body mass index (BMI) 31.5 kg/m(2) ]; obese patients who maintained stable weight during the same time period (obese group, BMI 42.5 kg/m(2) ); and normal-weight subjects (lean group, BMI 24.4 kg/m(2) ). Patients in the surgery group, compared to those in the obese group, had slightly lower common carotid artery (CCA) IMT (0.75 ± 0.18 vs. 0.78 ± 0.17 mm) and common carotid bulb (CCB) IMT (0.92 ± 0.32 vs. 0.97 ± 0.32 mm); however, these differences were not statistically significant. Lean individuals, compared with those in the surgery group, had significantly lower CCA and CCB IMT values (P < 0.001). In forward stepwise multiple regression analyses including all subjects (n = 132), CCA IMT was predicted mainly by visceral adipose tissue, but was also related to blood pressure and levels of triglycerides and high-sensitivity C-reactive protein. Carotid lumen diameter was primarily influenced by lean body mass. Visceral adiposity was the main determinant of premature carotid artery atherosclerosis, possibly through elevated blood pressure, dyslipidaemia and inflammation. Lean body mass predicted carotid artery lumen diameter. Obese patients with long-term sustained weight loss did not have thinner carotid artery walls compared to their weight-stable obese counterparts. This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 12/2013; DOI:10.1111/joim.12171 · 5.79 Impact Factor
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    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.
    Obesity 12/2013; 21(12). DOI:10.1002/oby.20443 · 4.39 Impact Factor
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    ABSTRACT: OBJECTIVE: Increased sensitivity to alcohol after gastric bypass has been described. The aim of this study was to investigate whether bariatric surgery is associated with alcohol problems. DESIGN AND METHODS: The prospective, controlled Swedish Obese Subjects (SOS) study enrolled 2010 obese patients who underwent bariatric surgery (68% vertical banded gastroplasty (VBG), 19% banding and 13% gastric bypass) and 2037 matched controls. Patients were recruited between 1987 and 2001. Data on alcohol abuse diagnoses, self-reported alcohol consumption and alcohol problems were obtained from the National Patient Register and questionnaires. Follow-up time was 8-22 years. RESULTS: During follow-up, 93.1 % of the surgery patients and 96.0 % of the controls reported alcohol consumption classified as low risk by the World Health Organization (WHO). However, compared to controls, the gastric bypass group had increased risk of alcohol abuse diagnoses (adjusted hazard ratio [adjHR] = 4.97), alcohol consumption at least at the WHO medium risk level (adjHR = 2.69) and alcohol problems (adjHR = 5.91). VBG increased risk of these conditions with adjHRs of 2.23, 1.52 and 2.30, respectively, while banding was not different from controls. CONCLUSIONS: We conclude that alcohol consumption, alcohol problems and alcohol abuse are increased after gastric bypass and VBG.
    Obesity 12/2013; 21(12). DOI:10.1002/oby.20397 · 4.39 Impact Factor
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    ABSTRACT: OBJECTIVE: Obesity is frequently associated with obstructive sleep apnea (OSA). Both conditions are proinflammatory and proposed to deteriorate cardiac function. We used a nested cohort study design to evaluate the long-term impact of bariatric surgery on OSA and how weight loss and OSA relate to inflammation and cardiac performance. DESIGN AND METHODS: At 10-year follow-up in the Swedish Obese Subjects (SOS) study, we identified 19 obese subjects (BMI 31.2 ± 5.3 kg m(-2) ), who following bariatric surgery at SOS-baseline had displayed sustained weight losses (surgery group), and 20 obese controls (BMI 42.0 ± 6.2 kg m(-2) ), who during the same time-period had maintained stable weight (control group). All study participants underwent overnight polysomnography examination, echocardiography and analysis of inflammatory markers. RESULTS: The surgery group displayed a lower apnea hypopnea index (AHI) (19.9 ± 21.5 vs. 37.8 ± 27.7 n/h, P = 0.013), lower inflammatory activity (hsCRP 2.3 ± 3.0 vs. 7.2 ± 5.0 mg L(-1) , P < 0.001), reduced left ventricular mass (165 ± 22 vs. 207 ± 22 g, P < 0.001) and superior left ventricular diastolic function (E/A ratio 1.24 ± 1.10 vs. 1.05 ± 0.20, P = 0.006) as compared with weight stable obese controls. In multiple regression analyses including all subjects (n = 39) and controlling for BMI, the AHI remained independently associated with hsCRP (β = 0.09, P < 0.001), TNF-α (β = 0.03, P = 0.031), IL-6 (β = 0.01, P = 0.007), IL 10 (β = -0.06; P = 0.018), left ventricular mass (β = 0.64, P < 0.001), left atrial area (β = 0.08, P = 0.002), pulmonary artery pressure (β = 0.08, P = 0.011) and E/Ea ratio (β = 0.04, P = 0.021). CONCLUSIONS: Patients with sustained weight loss after bariatric surgery display less severe sleep apnea, reduced inflammatory activity, and enhanced cardiac function. Persisting sleep apnea appears to limit the beneficial effect of weight loss on inflammation and cardiac performance.
    Obesity 04/2013; 21(4):698-704. DOI:10.1002/oby.20115 · 4.39 Impact Factor
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    ABSTRACT: Obesity is associated with elevated serum transaminase levels and non-alcoholic fatty liver disease and weight loss is a recommended therapeutic strategy. Bariatric surgery is effective in obtaining and maintaining weight loss. Aim of the present study was to examine the long-term effects of bariatric surgery on transaminase levels in obese individuals. The Swedish Obese Subjects (SOS) study is a prospective controlled intervention study designed to compare the long-term effects of bariatric surgery and usual care in obese subjects. A total of 3,570 obese participants with no excess of alcohol consumption at baseline (1,795 and 1,775 in the control and surgery group, respectively) were included in the analyses. Changes in transaminase levels during follow-up were compared in the surgery and control groups. Compared to usual care, bariatric surgery was associated with lower serum ALT and AST levels at 2- and 10- year follow up. The reduction in ALT levels was proportional to the degree of weight loss. Both the incidence of and the remission from high transaminase levels were more favorable in the surgery group compared to the control group. Similarly, the prevalence of ALT/AST ratio <1 was lower in the surgery compared to the control group at both 2- and 10-year follow up. Bariatric surgery results in a sustained reduction in transaminase levels and a long-term benefit in obese individuals.
    PLoS ONE 03/2013; 8(3):e60495. DOI:10.1371/journal.pone.0060495 · 3.53 Impact Factor
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    ABSTRACT: Context:Obesity and insulin resistance are risk factors for cancer development. The IRS1 rs2943641 genetic variant has been widely associated with insulin resistance.Objective:The aim of the study was to examine whether the IRS1 rs2943641 associates with cancer incidence in obese individuals.Design, Setting and Patients:The IRS1 rs2943641 was genotyped in participants from the Swedish Obese Subjects (SOS) study, an intervention trial on the effect of bariatric surgery on mortality and morbidity compared with usual care and in the population-based Malmö Diet and Cancer (MDC) cohort. In both studies, the median follow-up for cancer incidence was about 15 years.Intervention and Main Outcome Measure:Cancer incidence was assessed in both the SOS and the MDC cohorts through national and local registers.Results:The IRS1 T allele was associated with lower insulin resistance in both the SOS and the MDC studies. A lower cancer incidence was found in T allele carriers from the SOS control group (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.62-0.96; P = .021) and was restricted to morbidly obese individuals (HR 0.67, 95% CI 0.50-0.91; P = .011). No evidence of such association was detected in the surgery group (interaction P = .005). In the MDC cohort, a nonsignificant tendency for lower cancer incidence in T allele carriers was observed only in morbidly obese individuals. A meta-analysis of morbidly obese individuals (body mass index > 40 kg/m(2)) from the two cohorts strengthened the evidence for the association (HR 0.66, 95% CI 0.50-0.87; P = .004).Conclusions:Our results suggest that the T allele of rs2943641 near IRS1 may associate with lower cancer incidence in morbidly obese individuals.
    The Journal of Clinical Endocrinology and Metabolism 02/2013; 98(4). DOI:10.1210/jc.2012-2831 · 6.31 Impact Factor
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    ABSTRACT: OBJECTIVE Patients with a BMI <35 kg/m(2) and patients with a BMI between 35 and 40 kg/m(2) without comorbidities are noneligible by current eligibility criteria for bariatric surgery. We used Swedish obese subjects (SOS) to explore long-term outcomes in noneligible versus eligible patients.RESEARCH DESIGN AND METHODS The SOS study involved 2,010 obese patients who underwent bariatric surgery (68% vertical-banded gastroplasty, 19% banding, and 13% gastric bypass) and 2,037 contemporaneously matched obese controls receiving usual care. At inclusion, the participant age was 37-60 years and BMI was ≥34 kg/m(2) in men and ≥38 kg/m(2) in women. The effect of surgery was assessed in patients that do (n = 3,814) and do not (n = 233) meet current eligibility criteria. The date of analysis was 1 January 2012. The follow-up time was up to 20 years, with a median of 10 years.RESULTSCardiovascular risk factors were significantly improved both in noneligible and eligible individuals after 10 years of follow-up. Surgery reduced the diabetes incidence in both the noneligible (adjusted hazard ratio 0.33 [95% CI 0.13-0.82], P = 0.017) and eligible (0.27 [0.22-0.33], P < 0.001) groups. We could not detect a difference in the effect of surgery between the groups (adjusted interaction P value = 0.713).CONCLUSIONS Bariatric surgery drastically reduced the incidence of type 2 diabetes both in noneligible and eligible patients and improved cardiovascular risk factors in both groups. Our results show that strict BMI cutoffs are of limited use for bariatric surgery prioritization if the aim is to prevent diabetes and improve cardiovascular risk factors.
    Diabetes care 01/2013; 36(5). DOI:10.2337/dc12-1395 · 8.57 Impact Factor
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    ABSTRACT: Context:Men and women differ in body fat distribution and adipose tissue metabolism as well as in obesity comorbidities and their response to obesity treatment.Objective:The objective of the study was a search for sex differences in adipose tissue function.Design and Setting:This was an exploratory study performed at a university hospital.Participants and Main Outcome Measures:Resting metabolic rate (RMR), body composition, and sc adipose tissue genome-wide expression were measured in the SOS Sib Pair study (n = 732).Results:The relative contribution of fat mass to RMR and the metabolic rate per kilogram adipose tissue was higher in women than in men (P value for sex by fat mass interaction = .0019). Women had increased expression of genes involved in mitochondrial function, here referred to as a mitochondrial gene signature. Analysis of liver, muscle, and blood showed that the pronounced mitochondrial gene signature in women was specific for adipose tissue. Brown adipocytes are dense in mitochondria, and the expression of the brown adipocyte marker uncoupling protein 1 was 5-fold higher in women compared with men in the SOS Sib Pair Study (P = 7.43 × 10(-7)), and this was confirmed in a cross-sectional, population-based study (n = 83, 6-fold higher in women, P = .00256).Conclusions:The increased expression of the brown adipocyte marker uncoupling protein 1 in women indicates that the higher relative contribution of the fat mass to RMR in women is in part explained by an increased number of brown adipocytes.
    The Journal of Clinical Endocrinology and Metabolism 12/2012; 98(2). DOI:10.1210/jc.2012-2764 · 6.31 Impact Factor
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    ABSTRACT: Obesity and SLC2A9 genotype are strong determinants of uric acid levels. However, data on SLC2A9 variants and weight loss induced changes in uric acid levels are missing. We examined whether the changes in uric acid levels two- and ten-years after weight loss induced by bariatric surgery were associated with SLC2A9 single nucleotide polymorphisms (SNPs) in the Swedish Obese Subjects study. SNPs (N = 14) identified by genome-wide association studies and exonic SNPs in the SLC2A9 gene locus were genotyped. Cross-sectional associations were tested before (N = 1806), two (N = 1664) and ten years (N = 1201) after bariatric surgery. Changes in uric acid were compared between baseline and Year 2 (N = 1660) and years 2 and 10 (N = 1172). A multiple testing corrected threshold of P = 0.007 was used for statistical significance. Overall, 11 of the 14 tested SLC2A9 SNPs were significantly associated with cross-sectional uric acid levels at all three time points, with rs13113918 showing the strongest association at each time point (R(2) = 3.7-5.2%, 3.9×10(-22)≤p≤7.7×10(-11)). One SNP (rs737267) showed a significant association (R(2) = 0.60%, P = 0.002) with change in uric acid levels from baseline to Year 2, as common allele homozygotes (C/C, N = 957) showed a larger decrease in uric acid (-61.4 µmol/L) compared to minor allele carriers (A/X: -51.7 µmol/L, N = 702). No SNPs were associated with changes in uric acid from years 2 to 10. SNPs in the SLC2A9 locus contribute significantly to uric acid levels in obese individuals, and the associations persist even after considerable weight loss due to bariatric surgery. However, we found little evidence for an interaction between genotype and weight change on the response of uric acid to bariatric surgery over ten years. Thus, the fluctuations in uric acid levels among the surgery group appear to be driven by the weight losses and gains, independent of SLC2A9 genotypes.
    PLoS ONE 12/2012; 7(12):e51658. DOI:10.1371/journal.pone.0051658 · 3.53 Impact Factor

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22k Citations
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Institutions

  • 1971–2015
    • University of Gothenburg
      • • Institute of Medicine
      • • Department of Molecular and Clinical Medicine
      • • Department of Anesthesiology and Intensive care
      • • Department of Surgery
      • • Department of Clinical Nutrition
      Goeteborg, Västra Götaland, Sweden
  • 1970–2013
    • Sahlgrenska University Hospital
      • Department of Cardiology
      Goeteborg, Västra Götaland, Sweden
  • 2010
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
  • 2007
    • University of Cambridge
      Cambridge, England, United Kingdom
    • Helsingborgs Lasarett
      Hälsingborg, Skåne, Sweden
  • 1996–2005
    • Laval University
      • Département de Médecine Sociale et Préventive
      Québec, Quebec, Canada
  • 2002
    • Pennington Biomedical Research Center
      • Human Genomics Laboratory
      Baton Rouge, Louisiana, United States
  • 2001
    • University of Oulu
      • Department of Internal Medicine
      Uleoborg, Northern Ostrobothnia, Finland
  • 2000
    • Saint Luke's Hospital (NY, USA)
      New York City, New York, United States
  • 1999
    • Uppsala University Hospital
      Uppsala, Uppsala, Sweden
  • 1980
    • Lund University
      Lund, Skåne, Sweden