Strong In-Plane Magnetization and Spin Polarization in (Co0.15Fe0.85)5GeTe2/Graphene van der Waals Heterostructure Spin-Valve at Room Temperature.

Van der Waals (vdW) magnets are promising, because of their tunable magnetic properties with doping or alloy composition, where the strength of magnetic interactions, their symmetry, and magnetic anisotropy can be tuned according to the desired application. However, so far, most of the vdW magnet-based spintronic devices have been limited to cryogenic temperatures with magnetic anisotropies favoring out-of-plane or canted orientation of the magnetization. Here, we report beyond room-temperature lateral spin-valve devices with strong in-plane magnetization and spin polarization of the vdW ferromagnet (Co0.15Fe0.85)5GeTe2 (CFGT) in heterostructures with graphene. Density functional theory (DFT) calculations show that the magnitude of the anisotropy depends on the Co concentration and is caused by the substitution of Co in the outermost Fe layer. Magnetization measurements reveal the above room-temperature ferromagnetism in CFGT and clear remanence at room temperature. Heterostructures consisting of CFGT nanolayers and graphene were used to experimentally realize basic building blocks for spin valve devices, such as efficient spin injection and detection. Further analysis of spin transport and Hanle spin precession measurements reveals a strong in-plane magnetization with negative spin polarization at the interface with graphene, which is supported by the calculated spin-polarized density of states of CFGT. The in-plane magnetization of CFGT at room temperature proves its usefulness in graphene lateral spin-valve devices, thus revealing its potential application in spintronic technologies.

Bariatric Surgery and the Risk of New-Onset Atrial Fibrillation in Swedish Obese Subjects.

BACKGROUND: Obesity is a risk factor for atrial fibrillation, which in turn is associated with stroke, heart failure, and increased all-cause mortality. OBJECTIVES: The authors investigated whether weight loss through bariatric surgery may reduce the risk of new-onset atrial fibrillation. METHODS: SOS (Swedish Obese Subjects) is a prospective matched cohort study conducted at 25 surgical departments and 480 primary healthcare centers in Sweden. The cohort was recruited between 1987 and 2001. Among 4,021 obese individuals with sinus rhythm and no history of atrial fibrillation, 2,000 underwent bariatric surgery (surgery group), and 2,021 matched obese control subjects received usual care (control group). The outcome, first-time atrial fibrillation, was ascertained by crosschecking the SOS database with the Swedish National Patient Register on inpatient and outpatient diagnosis codes. RESULTS: During a median follow-up of 19 years, first time atrial fibrillation occurred in 247 patients (12.4%) in the surgical group, and in 340 (16.8%) control subjects. The risk of developing atrial fibrillation was 29% lower in the surgery group versus the control group (hazard ratio: 0.71; 95% confidence interval: 0.60 to 0.83; p < 0.001). Younger individuals benefited more from surgical intervention than those who were older (p value for interaction 0.001). Also, those with a high diastolic blood pressure benefitted more from surgery than did those with a low diastolic blood pressure (p for interaction = 0.028). CONCLUSIONS: Compared with usual care, weight loss through bariatric surgery reduced the risk of atrial fibrillation among persons being treated for severe obesity. The risk reduction was more apparent in younger people and in those with higher blood pressure.

Determinants of Diabetes Remission and Glycemic Control After Bariatric Surgery.

OBJECTIVE: Eligibility criteria for bariatric surgery in diabetes include BMI ≥35 kg/m(2) and poorly controlled glycemia. However, BMI does not predict diabetes remission, and thus, predictors need to be identified. RESEARCH DESIGN AND METHODS: Seven hundred twenty-seven patients were included in a database merged from the Swedish Obese Subjects (SOS) study and two randomized controlled studies, with 415 surgical and 312 medical patients in total. Bariatric operations were divided into gastric only (GO) and gastric plus diversion (GD). RESULTS: Sixty-four percent of patients in the surgical arm and 15.0% in the medical arm experienced diabetes remission (P < 0.001). GO yielded 60% remission, and GD yielded 76% remission. The best predictors of diabetes remission were lower baseline glycemia and shorter diabetes duration. However, when operation type was considered, GD predicted a higher likelihood of remission and greater weight loss. Patients in remission (responders) lost more weight (25% vs. 17%) and waist circumference (18% vs. 13%) and experienced better insulin sensitivity than nonresponders. CONCLUSIONS: Surgery is more effective than medical treatment in achieving diabetes remission and tighter glycemic control. Shorter diabetes duration, lower fasting glycemia before surgery, and GD versus GO procedures independently predict higher rates of remission, whereas baseline HbA1c and waist circumference predict improved glycemic control. The results show the advantage of an early operation together with better controlled glycemia on diabetes remission independently of BMI.

Health-care costs over 15 years after bariatric surgery for patients with different baseline glucose status: results from the Swedish Obese Subjects study.

BACKGROUND: Bariatric surgery prevents and induces remission of type 2 diabetes in many patients. The effect of preoperative glucose status on long-term health-care costs is unknown. We aimed to assess health-care costs over 15 years for patients with obesity treated conventionally or with bariatric surgery and who had either euglycaemia, prediabetes, or type 2 diabetes before intervention. METHODS: The Swedish Obese Subjects (SOS) study is a prospective study of adults who had bariatric surgery and contemporaneously matched controls who were treated conventionally (age 37-60 years; BMI of ≥34 in men and ≥38 in women) recruited from 25 Swedish surgical departments and 480 primary health-care centres. Exclusion criteria were identical for both study groups, and were previous gastric or bariatric surgery, recent malignancy or myocardial infarction, selected psychiatric disorders, and other contraindicating disorders to bariatric surgery. Conventional treatment ranged from no treatment to lifestyle intervention and behaviour modification. In this study, we retrieved prescription drug costs for the patients in the SOS study via questionnaires and the nationwide Swedish Prescribed Drug Register. We retrieved data for inpatient and outpatient visits from the Swedish National Patient Register. We followed up the sample linked to register data for up to 15 years. We adjusted mean differences for baseline characteristics. Analyses were by intention to treat. The SOS study is registered with ClinicalTrials.gov, number NCT01479452. FINDINGS: Between Sept 1, 1987, and Jan 31, 2001, 2010 adults who had bariatric surgery and 2037 who were treated conventionally were enrolled into the SOS study. In this study, we followed up 4030 patients (2836 who were euglycaemic; 591 who had prediabetes; 603 who had diabetes). Drug costs did not differ between the surgery and conventional treatment groups in the euglycaemic subgroup (surgery US$10,511 vs conventional treatment $10,680; adjusted mean difference -$225 [95% CI -2080 to 1631]; p=0·812), but were lower in the surgery group in the prediabetes ($10,194 vs $13,186; -$3329 [-5722 to -937]; p=0·007) and diabetes ($14,346 vs $19,511; -$5487 [-7925 to -3049]; p<0·0001) subgroups than in the conventional treatment group. Compared with the conventional treatment group, we noted greater inpatient costs in the surgery group for the euglycaemic ($51,225 vs $25,313; $22,931 [19,001-26,861]; p<0·0001), prediabetes ($58,699 vs $32,861; $27,152 [18,736-35,568]; p<0·0001), and diabetes ($61,569 vs $47,569; 18,697 [9992-27,402]; p<0·0001) subgroups. We noted no differences in outpatient costs. Total health-care costs were higher in the surgery group in the euglycaemic ($71,059 vs $45,542; $22,390 [17,358-27,423]; p<0·0001) and prediabetes ($78,151 vs $54,864; $26,292 [16,738-35,845]; p<0·0001) subgroups than in the conventional treatment group, whereas we detected no difference between treatment groups in patients with diabetes ($88,572 vs $79,967; $9081 [-1419 to 19,581]; p=0·090). INTERPRETATION: Total health-care costs were higher for patients with euglycaemia or prediabetes in the surgery group than in the conventional treatment group, but we detected no difference between the surgery and conventional treatment groups for patients with diabetes. Long-term health-care cost results support prioritisation of patients with obesity and type 2 diabetes for bariatric surgery. FUNDING: AFA Försäkring and Swedish Scientific Research Council.

Roux-en-Y Gastric Bypass Surgery Increases Respiratory Quotient and Energy Expenditure during Food Intake.

OBJECTIVE: The mechanisms determining long-term weight maintenance after Roux-en-Y gastric bypass (RYGB) remain unclear. Cross sectional studies have suggested that enhanced energy expenditure (EE) may play a significant role and the aim of this study was to reveal the impact of RYGB on each major component constituting total EE. DESIGN: Six obese female subjects, without other co-morbidities, were assessed before and at 10 days, 3 and 20 months after RYGB. Indirect calorimetry in a metabolic chamber was used to assess 24 h EE at each study visit. Other measurements included body composition by DEXA, gut hormone profiles and physical activity (PA) using high sensitivity accelerometers. RESULTS: Median Body Mass Index decreased from 41.1 (range 39.1-44.8) at baseline to 28 kg/m2 (range 22.3-30.3) after 20 months (p<0.05). Lean tissue decreased from 55.9 (range 47.5-59.3) to 49.5 (range 41.1-54.9) kg and adipose tissue from 61 (range 56-64.6) to 27 (range 12-34.3) kg (both p<0.05). PA over 24 h did not change after surgery whereas 24 h EE and basal metabolic rate (BMR) decreased. EE after a standard meal increased after surgery when adjusted for total tissue (p<0.05). After an initial drop, RQ (respiratory quotient) had increased at 20 months, both as measured during 24 h and after food intake (p<0.05). CONCLUSION: RYGB surgery up-regulates RQ and EE after food intake resulting in an increased contribution to total EE over 24 h when corrected for total tissue.

Incidence and remission of type 2 diabetes in relation to degree of obesity at baseline and 2 year weight change: the Swedish Obese Subjects (SOS) study.

AIMS/HYPOTHESIS: The aim of this work was to analyse the rates of incidence and remission of type 2 diabetes in relation to baseline BMI and weight change in the prospective, controlled Swedish Obese Subjects (SOS) study. METHODS: Three-thousand four-hundred and eighty-five obese individuals receiving bariatric surgery or conventional treatment were grouped into four baseline BMI categories (<35, 35-40, 40-45 or ≥ 45 kg/m(2)) and five weight-change categories according to their BMI at 2 years (increase [≥ 1 BMI unit increase], no change [less than 1 BMI unit change], minor reduction [-1 to -9 BMI units], medium reduction [-10 to -14 BMI units] and major reduction [< -15 BMI units]). The incidence and remission of diabetes at 2 years was assessed. RESULTS: Among individuals with no weight change, diabetes incidence rates were 5.5%, 7.4%, 8.3% and 5.2%, in the four baseline BMI categories, respectively. In those with an initial BMI of 35-40, 40-45 and ≥ 45 kg/m(2) who attained a minor reduction in weight, the corresponding rates were 1.3%, 1.2% and 3.4%, respectively. In both the medium- and major-weight-reduction groups, diabetes incidence was ≤ 0.5%. Among individuals with diabetes at baseline, the remission rates were 15.3-26.9% in the no-weight-change groups, and 48.1-70% for individuals who attained a minor weight reduction. In the medium- and major-weight-reduction groups, the remission rate was 77-97%. There were no differences in 2 year incidence and remission rates between different baseline BMI groups that achieved the same degree of weight reduction. CONCLUSIONS/INTERPRETATION: In obese individuals, the favourable effect of weight reduction on type 2 diabetes incidence and remission is independent of initial BMI. Trial registration ClinicalTrials.gov number NCT01479452.

Dietary patterns, cardiometabolic risk factors, and the incidence of cardiovascular disease in severe obesity.

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/m(2) 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. RESULTS: An 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 [ß (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.

Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease.

UNLABELLED: Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very-low-density lipoproteins (VLDLs). 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 NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1,819 controls from the Swedish Obese Subjects (SOS) 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 NASH (odds ratio [OR]: 1.84; 95% confidence interval [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 SOS cohort, E167K carriers had higher alanine aminotransferase ALT and lower lipid levels (P < 0.05), as well as a lower incidence of cardiovascular events (hazard ratio: 0.61; 95% CI: 0.39-0.95). CONCLUSIONS: Carriers of the TM6SF2 E167K variant are more susceptible to progressive NASH, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export VLDLs is deleterious for the liver.

Psychological aspects of eating behavior as predictors of 10-y weight changes after surgical and conventional treatment of severe obesity: results from the Swedish Obese Subjects intervention study.

BACKGROUND: There is a need for a better understanding of the factors that influence long-term weight outcomes after bariatric surgery. OBJECTIVE: 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. DESIGN: 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. RESULTS: 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 (ß = 0.13-0.29, P < 0.01 in men; ß = 0.11-0.28, P < 0.001 in women) and experienced larger 1-y decreases in these behaviors (ß = 0.31-0.48, P < 0.001 in men; ß = 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. CONCLUSION: 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.

The GH receptor exon 3 deleted/full-length polymorphism is associated with central adiposity in the general population.

OBJECTIVE: To test the hypothesis that the GH receptor (GHR) exon 3 deleted (d3)/full-length (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 subgroup 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 years. The MDC-CC includes 5451 successfully genotyped subjects (41.5% men), with an average age of 57.5 years. 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 ∼4 kg more (P=0.011), and had larger waist-to-hip ratio (WHR, P=0.036), larger waist circumference (P=0.016), and more fat-free mass estimated from total body potassium (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.

Association of bariatric surgery with long-term remission of type 2 diabetes and with microvascular and macrovascular complications.

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.

Tracking of a dietary pattern and its components over 10-years in the severely obese.

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/m(2)). 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.

Low copy number of the salivary amylase gene predisposes to obesity.

Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10(-14)) and serum enzyme levels (P < 2.20 × 10(-16)), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = -0.15 (0.02) kg/m(2); P = 6.93 × 10(-10)) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13-1.26; P = 1.46 × 10(-10)). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.

Adiponectin and bariatric surgery: associations with diabetes and cardiovascular disease in the Swedish Obese Subjects Study.

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. RESULTS: In 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.

Sleep apnea modifies the long-term impact of surgically induced weight loss on cardiac function and inflammation.

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 (ß = 0.09, P < 0.001), TNF-α (ß = 0.03, P = 0.031), IL-6 (ß = 0.01, P = 0.007), IL 10 (ß = -0.06; P = 0.018), left ventricular mass (ß = 0.64, P < 0.001), left atrial area (ß = 0.08, P = 0.002), pulmonary artery pressure (ß = 0.08, P = 0.011) and E/Ea ratio (ß = 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.

Long-term effect of bariatric surgery on liver enzymes in the Swedish Obese Subjects (SOS) study.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Bariatric surgery results in a sustained reduction in transaminase levels and a long-term benefit in obese individuals.

Alcohol consumption and alcohol problems after bariatric surgery in the Swedish obese subjects study.

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 2,010 obese patients who underwent bariatric surgery (68% vertical banded gastroplasty (VBG), 19% banding, and 13% gastric bypass) and 2,037 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 the risk of these conditions with adjHRs of 2.23, 1.52, and 2.30, respectively, while banding was not different from controls. CONCLUSIONS: Alcohol consumption, alcohol problems, and alcohol abuse are increased after gastric bypass and VBG.

The IRS1 rs2943641 variant and risk of future cancer among morbidly obese individuals.

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.

Evaluation of current eligibility criteria for bariatric surgery: diabetes prevention and risk factor changes in the Swedish obese subjects (SOS) study.

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. RESULTS: Cardiovascular 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.

Adipose tissue resting energy expenditure and expression of genes involved in mitochondrial function are higher in women than in men.

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.