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Background Weight loss improves fatty liver disease. No randomized trial has compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on liver fat content and fibrosis. Objective To compare the 1-year effects of SG and RYGB on hepatic steatosis and fibrosis. Design Single-center, randomized, controlled trial (Oseberg [ObesitySurgery in Tonsberg]). (ClinicalTrials.gov: NCT01778738). Setting Tertiary care obesity center in Norway. Participants 100 patients (65% female; mean age, 47.5 years; mean body mass index, 42 kg/m2) with type 2 diabetes mellitus (T2DM). Intervention From January 2013 to February 2018, patients were randomly assigned (1:1 ratio) to SG or RYGB. Measurements The primary outcome was remission of T2DM (previously published). Predefined secondary outcomes in the present study were hepatic steatosis and fibrosis assessed by magnetic resonance imaging (liver fat fraction), enhanced liver fibrosis (ELF) test, noninvasive indices, and liver enzymes. Results Liver fat fraction declined similarly after SG (-19.7% [95% CI, -22.5% to -16.9%]) and RYGB (-21.5% [CI, -24.3% to -18.6%]) from surgery to 1-year follow-up, and almost all patients (SG, 94%; RYGB, 100%) had no or low-grade steatosis at 1 year. The ELF score category remained stable in 77% of patients, but 18% experienced worsening of fibrosis at 1 year, with no substantial between-group difference. Limitations Single-center study, short follow-up time, and lack of power for secondary outcomes. Conclusion With an almost complete clearance of liver fat 1 year after surgery, RYGB and SG were both highly effective in reducing hepatic steatosis. Bariatric surgery had less influence on degree of fibrosis in the short term, but assessment of long-term progression is warranted. Primary funding source Vestfold Hospital Trust and the South-Eastern Norway Regional Health Authority.

Chronic local inflammation of adipose tissue is an important feature of obesity. Serglycin is a proteoglycan highly expressed by various immune cell types known to infiltrate adipose tissue under obese conditions. To investigate if serglycin expression has an impact on diet-induced adipose tissue inflammation, we subjected Srgn+/+ and Srgn−/− mice (C57BL/6J genetic background) to an 8-wk high-fat and high-sucrose diet. The total body weight was the same in Srgn+/+ and Srgn−/− mice after diet treatment. Expression of white adipose tissue genes linked to inflammatory pathways were lower in Srgn−/− mice. We also noted reduced total macrophage abundance, a reduced proportion of proinflammatory M1 macrophages, and reduced formation of crown-like structures in adipose tissue of Srgn−/− compared with Srgn+/+ mice. Further, Srgn−/− mice had more medium-sized adipocytes and fewer large adipocytes. Differentiation of preadipocytes into adipocytes (3T3-L1) was accompanied by reduced Srgn mRNA expression. In line with this, analysis of single-cell RNA sequencing data from mouse and human adipose tissue supports that Srgn mRNA is predominantly expressed by various immune cells, with low expression in adipocytes. Srgn mRNA expression was higher in obese compared with lean humans and mice, accompanied by an increased expression of immune cell gene markers. SRGN and inflammatory marker mRNA expression was reduced upon substantial weight loss in patients after bariatric surgery. Taken together, this study introduces a role for serglycin in the regulation of obesity-induced adipose inflammation.

Limited evidence suggests that surgical and non-surgical obesity treatment differentially influence plasma Lipoprotein (a) [Lp(a)] levels. Further, a novel association between plasma arachidonic acid and Lp(a) has recently been shown, suggesting that fatty acids are a possible target to influence Lp(a). Here, the effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) were compared, and it was examined whether the effects were mediated by changes in plasma fatty acid (FA) levels.The study includes two independent trials of patients with overweight or obesity. Trial 1: Two-armed intervention study including 82 patients who underwent a 7-week low energy diet (LED), followed by Roux-en-Y gastric bypass and 52-week follow-up (surgery-group), and 77 patients who underwent a 59-week energy restricted diet- and exercise-program (lifestyle-group). Trial 2: A clinical study including 134 patients who underwent a 20-week very-LED/LED (lifestyle-cohort).In the surgery-group, Lp(a) levels [median (interquartile range)] tended to increase in the pre-surgical LED-phase [17(7-68)-21(7-81)nmol/L, P = 0.05], but decreased by 48% after surgery [21(7-81)-11(7-56)nmol/L, P 0.001]. In the lifestyle-group and lifestyle-cohort, Lp(a) increased by 36%[14(7-77)-19(7-94)nmol/L, P 0.001] and 14%[50(14-160)-57(19-208)nmol/L, P 0.001], respectively. Changes in Lp(a) were independent of weight loss. Plasma levels of total saturated FAs remained unchanged after surgery, but decreased after lifestyle interventions. Arachidonic acid and total n-3 FAs decreased after surgery, but increased after lifestyle interventions. Plasma FAs did not mediate the effects on Lp(a).Bariatric surgery reduced, whereas lifestyle interventions increased plasma Lp(a), independent of weight loss. The interventions differentially influenced changes in plasma FAs, but these changes did not mediate changes in Lp(a).Trial 1: Clinicaltrials.gov NCT00626964. Trial 2: Netherlands Trial Register NL2140 (NTR2264).

Type 2 diabetes (T2DM) is associated with gastroesophageal reflux disease (GERD) in the general population, but the relationship between these conditions in candidates for bariatric surgery is uncertain. We compared the prevalence of GERD and the association between GERD symptoms and esophagitis among bariatric candidates with and without T2DM. Cross-sectional study of baseline data from the Oseberg study in Norway. Both groups underwent gastroduodenoscopy and completed validated questionnaires: Gastrointestinal Symptom Rating Scale and Gastroesophageal Reflux Disease Questionnaire. Participants with T2DM underwent 24-h pH-metry. A total of 124 patients with T2DM, 81 women, mean (SD) age 48.6 (9.4) years and BMI 42.3 (5.5) kg/m2, and 64 patients without T2DM, 46 women, age 43.0 (11.0) years and BMI 43.0 (5.0) kg/m2, were included. The proportions of patients reporting GERD-symptoms were low (

Prediction of type 2 diabetes (T2DM) remission is an important part of risk-benefit assessment before bariatric surgery.Advanced-DiaRem (Ad-DiaRem) and ABCD diabetes remission scores for sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) were calculated using baseline data. Differences in model discrimination using area under the curve of receiver operating curve (AUC-ROC) and model calibration were tested for complete remission (HbA1c ≤ 6.0% without antidiabetic medications) in the two groups. Optimal cutoff scores were calculated using the Youden index.We randomized 109 patients to either SG or RYGB. With one patient lost to follow-up in each group, the scores were calculated for 54 patients in the SG group and 53 patients in the RYGB group. Both models showed moderate predictive power without any significant difference between the groups: AUC-ROCs (95% CI) for the Ad-DiaRem score (SG versus RYGB) were 0.872 (0.780-0.964) versus 0.843 (0.733-0.954), p = 0.69, and for the ABCD score 0.849 (0.752-0.946) versus 0.750 (0.580-0.920), p = 0.32, respectively. Using optimal cutoff points derived from the whole study population, the actual proportion of diabetes remission was significantly higher than predicted for both the Ad-DiaRem and ABCD scores in the RYGB group. Diabetes duration and glycated haemoglobin predicted diabetes remission in the entire Oseberg population.Both the Ad-DiaRem and ABCD scores showed moderate ability to discriminate between those who achieved remission of T2DM and those who did not after SG and RYGB. Larger studies are needed for the identification of procedure-specific optimal cutoffs. Trial Registration ClinicalTrials.gov Identifier: NCT01778738.

Objective This study aimed to compare the effects of two aerobic exercise programs of different intensities on energy expenditure. Methods This was a single‐center randomized controlled trial of patients with severe obesity allocated to a 24‐week moderate‐intensity continuous training (MICT) program or a combined MICT with high‐intensity interval training (HIIT/MICT) program. The primary outcome was energy expenditure during exercise (EEDE). Secondary outcomes included resting metabolic rate, cardiorespiratory fitness, and body composition. Results A total of 82 (56% females) patients were screened, and 71 (55% females) patients were allocated to HIIT/MICT (n = 37) or MICT (n = 34). Per‐protocol analysis showed that EEDE increased by 10% (95% CI: 3%‐17%) in the HIIT/MICT group (n = 16) and 7.5% (95% CI: 4%‐10%) in the MICT group (n = 24), with no differences between groups. In the 8‐ to 16‐ week per‐protocol analysis, the HIIT/MICT group had a significantly larger increase in EEDE compared with the MICT group. Resting metabolic rate remained unchanged in both groups. HIIT/MICT and MICT were associated with significant weight loss of 5 kg and 2 kg, respectively. Conclusions Patients completing a 24‐week combined HIIT/MICT program did not achieve a higher EEDE compared with those who completed a 24‐week MICT program. The HIIT/MICT group experienced, on average, a 3‐kg‐larger weight loss than the MICT group. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Background and aims: Obesity with type-2 diabetes is a global challenge. Lifestyle interventions have limited effect for most patients. Bariatric surgery is highly effective, but resource-demanding, invasive and associated with serious complications. Recently, a new intragastric balloon was introduced, not requiring endoscopy for placement or removal (Elipse™, Allurion Inc., Natick, MA). The balloon is swallowed in a capsule and filled with water once in the stomach. The balloon self-deflates after 4 months and is naturally excreted. The present trial investigated balloon feasibility, safety and efficacy in patients with obesity and type-2 diabetes. Patients and methods: We treated 19 patients, with type-2 diabetes and body mass index (BMI) of 30.0-39.9 kg/m2 at two Norwegian centers with the Elipse balloon. Patient follow-up during balloon treatment mimicked real-world clinical practice, including dietary plan and outpatient visits. The primary efficacy endpoints were total body weight loss (TBWL) and HbA1c at weeks 16 and 52. Results: All patients underwent balloon insertion uneventfully as out-patients. Mean TBWL and HbA1c reduction after 16 and 52 weeks of balloon insertion was 3.9% (95%CI 2.1-5.7) and 0.8% (95%CI 1.9-3.5); and 7 (95%CI 4-10), and 1 (95%CI -6 to 9) mmol/mol, respectively. Adverse events occurred in two patients (10.5%): one developed gastric outlet obstruction, managed by endoscopic balloon removal; the other excessive vomiting and dehydration, managed conservatively. Conclusions: This first Scandinavian real-world clinical trial with a new minimally invasive intragastric balloon system demonstrated good feasibility, but did not confirm expected efficacy for weight loss and diabetes control.

BackgroundAlthough asthma and obesity are each associated with adverse respiratory outcomes, a possible interaction between them is less studied. This study assessed the extent to which asthma and overweight/obese status were independently associated with respiratory symptoms, lung function, Work Ability Score (WAS) and sick leave; and whether there was an interaction between asthma and body mass index (BMI) ≥25 kg/m2 regarding these outcomes.MethodsIn a cross-sectional study, 626 participants with physician-diagnosed asthma and 691 without asthma were examined. All participants completed a questionnaire and performed spirometry. The association of outcome variables with asthma and BMI category were assessed using regression models adjusted for age, sex, smoking status and education.ResultsAsthma was associated with reduced WAS (OR=1.9 (95% CI 1.4 to 2.5)), increased sick leave in the last 12 months (OR=1.4 (95% CI 1.1 to 1.8)) and increased symptom score (OR=7.3 (95% CI 5.5 to 9.7)). Obesity was associated with an increased symptom score (OR=1.7 (95% CI 1.2 to 2.4)). Asthma was associated with reduced prebronchodilator and postbronchodilator forced expiratory volume in 1 s (FEV1) (β=−6.6 (95% CI −8.2 to −5.1) and −5.2 (95% CI −6.7 to −3.4), respectively) and prebronchodilator forced vital capacity (FVC) (β=−2.3 (95% CI −3.6 to −0.96)). Obesity was associated with reduced prebronchodilator and postbronchodilator FEV1 (β=−2.9 (95% CI −5.1 to −0.7) and −2.8 (95% CI −4.9 to −0.7), respectively) and FVC (−5.2 (95% CI −7.0 to −3.4) and −4.2 (95% CI −6.1 to −2.3), respectively). The only significant interaction was between asthma and overweight status for prebronchodilator FVC (β=−3.6 (95% CI −6.6 to −0.6)).ConclusionsAsthma and obesity had independent associations with increased symptom scores, reduced prebronchodilator and postbronchodilator FEV1 and reduced prebronchodilator FVC. Reduced WAS and higher odds of sick leave in the last 12 months were associated with asthma, but not with increased BMI. Besides a possible association with reduced FVC, we found no interactions between asthma and increased BMI.

There is limited evidence for the effectiveness of bariatric surgery in adolescents, and the associated complications. The main objective of the 4XL study was to clarify whether laparoscopic Roux-en-Y gastric bypass (LGBP) combined with lifestyle intervention is a safe and effective treatment method.Data were retrieved from an ongoing non-randomised intervention study of adolescents with morbid obesity that is comparing the effects of gastric bypass combined with lifestyle intervention versus lifestyle intervention alone.Altogether 39 patients (64 % girls) treated with a gastric bypass, and 96 patients (57 % girls) treated with lifestyle intervention were examined prior to the start of treatment and one year later. The average age at inclusion (SD) was 16.7 (1.0) years vs. 15.6 (1.3) years, and average BMI was 45.6 (4.4) vs. 43.3 (4.1) kg/m2 in the two groups. Average (95 % CI) percentage weight loss was 30 % (27 %-33 %) after surgery versus weight gain of 1 % (-1 % to 3 %) in the control group. The difference between the groups was 31 % (95 % CI 27 %-34 %, p0.001). Cardiometabolic risk factors improved only after surgery. After gastric bypass, two early (6 weeks) minor complications were recorded. One year after surgery, 4 (10 %), 8 (21 %) and 4 (10 %) of patients had anaemia, iron deficiency or low vitamin B12 levels respectively, and 20 of 33 patients (61 %) had low two-hour blood glucose (2.8 mmol/l) after oral glucose tolerance testing.The results support previous studies showing that gastric bypass is associated with significant weight loss in adolescent patients with morbid obesity. The 4XL study is currently too small and the follow-up time too short to allow the risk of long-term complications to be assessed.

We examined complaints submitted to the Norwegian System of Patient Injury Compensation (NPE) following bariatric surgery, including the background for the complaint, the proportion of patients whose complaints were upheld, and the characteristics of complaints that were upheld.All complaints relating to bariatric surgery performed in the period 2012-18 were reviewed and categorised according to symptoms, findings and events relevant to the outcome of the complaint. Anonymous summaries from the experts' statements were reviewed and categorised according to year of decision, gender, age, basis for compensation or rejection, and whether the intervention was carried out in the public or private health service.Forty-four (26 %) of a total of 171 applications for patient injury compensation were upheld. These applications represented 25 patients who had surgery in the public health service (19 % upheld) and 19 patients who were operated on in the private health service (51 % upheld). The single most common reason for a complaint being upheld (n = 18) was lack of indication for bariatric surgery.More post-bariatric surgery complaints were upheld for lack of indication than for surgical errors. Proper patient selection, good preoperative preparation, good information and shared decision-making are important factors for achieving the best possible bariatric surgery outcome. An interdisciplinary team that monitors patients over time can help ensure the quality of the entire treatment chain.

Lifestyle interventions for children and adolescents with severe obesity show moderate short-term effects on weight reduction internationally. We evaluated treatment results at two Norwegian specialist outpatient clinics.We performed a retrospective analysis of data from children and adolescents between 3 and 18 years of age collected in 2012-2016. Children and adolescents with severe obesity who attended their one-year follow-up were included. We included in the analyses the following body weight measures: percentage overweight as defined by the International Obesity Task Force cut-off (% IOTF-25); BMI standard deviation score; waist circumference standard deviation score; and body fat percentage at the start of treatment and at one-year follow-up.Of 568 children and adolescents who started treatment, 416 (73 %) attended the one-year check-up. A total of 271 (65 %) patients achieved a reduction in %IOTF-25, while 228 patients (55 %) reduced their BMI standard deviation score. There was a statistically significant mean reduction of all four registered body weight measurements. Altogether 54 of 325 children (17 %) changed category from severe obesity to obesity, 8 (2 %) went from severe obesity to overweight, and 8 of 91 children (9 %) changed category from obesity to overweight or normal weight. The proportion of participants with a reduction of more than 5 % in %IOTF-25 was 43 % (177/416), and a reduction in BMI standard deviation score of more than 0.25 was observed in 23 % (95/416) of participants. Girls responded on average more poorly to the intervention than boys. There was no clinically significant difference in results between the treatment centres.After one year of treatment of children and adolescents with severe obesity in two specialist healthcare centres, we found a moderate mean reduction in weight, waist circumference and body fat percentage, but with large interindividual variation.

The Oseberg study demonstrated a higher one year remission rate of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) than after sleeve gastrectomy (SG). To explore mechanisms for the superiority of RYGB we assessed changes in glucose, C-peptide and incretin hormones after a 25 g OGTT and an IVGTT and calculated Disposition Indexes (DI) of beta cell function (DIIVGTT and DIOGTT). We used linear mixed models for repeated measures. Patients randomized to either RYGB (n=54) or SG (n=55), had a mean (SD) age of 48 (10) years, BMI 42.3 (5.3) kg/m², HbA1c 66 (18) mmol/mol, and 72 (66%) were women. OGTT and IVGTT were performed in 97% and 91% of patients respectively. At one year, the OGTT-derived glucose levels at 60-120 minutes were significantly lower after RYGB than after SG (all p Disclosure F. Fatima: Other Relationship; Self; South-Eastren Reagional Health Authority Norway. J. Hjelmesæth: Advisory Panel; Self; Novo Nordisk A/S. K.I. Birkeland: None. H.L. Gulseth: None. J.K. Hertel: None. M. Svanevik: None. R. Sandbu: None. B. Hartmann: None. J.J. Holst: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Spouse/Partner; Antag Therapeutics. D. Hofsø: None.

BACKGROUND We examined complaints submitted to the Norwegian System of Patient Injury Compensation (NPE) following bariatric surgery, including the background for the complaint, the proportion of patients whose complaints were upheld, and the characteristics of complaints that were upheld. MATERIAL AND METHOD All complaints relating to bariatric surgery performed in the period 2012-18 were reviewed and categorised according to symptoms, findings and events relevant to the outcome of the complaint. Anonymous summaries from the experts' statements were reviewed and categorised according to year of decision, gender, age, basis for compensation or rejection, and whether the intervention was carried out in the public or private health service. RESULTS Forty-four (26 %) of a total of 171 applications for patient injury compensation were upheld. These applications represented 25 patients who had surgery in the public health service (19 % upheld) and 19 patients who were operated on in the private health service (51 % upheld). The single most common reason for a complaint being upheld (n = 18) was lack of indication for bariatric surgery. INTERPRETATION More post-bariatric surgery complaints were upheld for lack of indication than for surgical errors. Proper patient selection, good preoperative preparation, good information and shared decision-making are important factors for achieving the best possible bariatric surgery outcome. An interdisciplinary team that monitors patients over time can help ensure the quality of the entire treatment chain.

Background Lifestyle interventions for children and adolescents with severe obesity show moderate short-term effects on weight reduction internationally. We evaluated treatment results at two Norwegian specialist outpatient clinics. Material and method We performed a retrospective analysis of data from children and adolescents between 3 and 18 years of age collected in 2012-2016. Children and adolescents with severe obesity who attended their one-year follow-up were included. We included in the analyses the following body weight measures: percentage overweight as defined by the International Obesity Task Force cut-off (% IOTF-25); BMI standard deviation score; waist circumference standard deviation score; and body fat percentage at the start of treatment and at one-year follow-up. Results Of 568 children and adolescents who started treatment, 416 (73 %) attended the one-year check-up. A total of 271 (65 %) patients achieved a reduction in %IOTF-25, while 228 patients (55 %) reduced their BMI standard deviation score. There was a statistically significant mean reduction of all four registered body weight measurements. Altogether 54 of 325 children (17 %) changed category from severe obesity to obesity, 8 (2 %) went from severe obesity to overweight, and 8 of 91 children (9 %) changed category from obesity to overweight or normal weight. The proportion of participants with a reduction of more than 5 % in %IOTF-25 was 43 % (177/416), and a reduction in BMI standard deviation score of more than 0.25 was observed in 23 % (95/416) of participants. Girls responded on average more poorly to the intervention than boys. There was no clinically significant difference in results between the treatment centres. Interpretation After one year of treatment of children and adolescents with severe obesity in two specialist healthcare centres, we found a moderate mean reduction in weight, waist circumference and body fat percentage, but with large interindividual variation.

Objectives Early obesity onset is a risk factor for specific comorbidities in adulthood, but whether this relationship is present in men and women with severe obesity is unknown. This study aimed to examine whether obesity onset in childhood or adolescence, as compared with adulthood, is associated with higher odds of comorbidities in men and women with severe obesity. Methods A cross-sectional study of treatment-seeking men and women with severe obesity attending a tertiary care centre in Norway, from 2006 to 2017, was performed. Results A total of 4,583 participants (69.13% women) were included. Almost all men (99.69%) and women (99.18%) suffered from ≥1 comorbidities. Compared with women, men were older (mean [SD]) (45.54 [12.14] vs. 42.56 [12.00] years, p 20 years), was associated with lower odds (OR [95% CI]) of obstructive sleep apnoea (OSA) in men (0.69 [0.53, 0.91], p

Background For patients with obesity and type 2 diabetes, weight loss improves insulin sensitivity and β-cell function, and can induce remission of diabetes. The comparative efficacy of various bariatric procedures for the remission of type 2 diabetes has not been fully elucidated. We aimed to compare the effects of the two most common bariatric procedures, gastric bypass and sleeve gastrectomy, on remission of diabetes and β-cell function. Methods We conducted a single-centre, triple-blind, randomised trial at Vestfold Hospital Trust (Tønsberg, Norway), in which patients (aged ≥18 years) with type 2 diabetes and obesity were randomly assigned (1:1) to receive gastric bypass or sleeve gastrectomy (the Oseberg study). Randomisation was performed with a computerised random number generator and a block size of 10. Treatment allocation was masked from participants, study personnel, and outcome assessors and was concealed with sealed opaque envelopes. Surgeons used identical skin incisions during both surgeries and were not involved in patient follow-up. The primary clinical outcome was the proportion of participants with complete remission of type 2 diabetes (HbA 1c of ≤6·0% [42 mmol/mol] without the use of glucose-lowering medication) at 1 year after surgery. The primary physiological outcome was disposition index (a measure of β-cell function) at 1 year after surgery, as assessed by an intravenous glucose tolerance test. Primary outcomes were analysed in the intention-to-treat and per-protocol populations. This trial is ongoing and closed to recruitment, and is registered with ClinicalTrials.gov, NCT01778738. Findings Between Oct 15, 2012, and Sept 1, 2017, 1305 patients who were preparing for bariatric surgery were screened, of whom 319 consecutive patients with type 2 diabetes were assessed for eligibility. 109 patients were enrolled and randomly assigned to gastric bypass (n=54) or sleeve gastrectomy (n=55). 107 (98%) of 109 patients completed 1-year follow-up, with one patient in each group withdrawing after surgery (per-protocol population). In the intention-to-treat population, diabetes remission rates were higher in the gastric bypass group than in the sleeve gastrectomy group (risk difference 27% [95% CI 10 to 44]; relative risk [RR] 1·57 [1·14 to 2·16], p=0·0054); results were similar in the per-protocol population (risk difference 27% [95% CI 10 to 45]; RR 1·57 [1·14 to 2·15], p=0·0036). In the intention-to-treat population, disposition index increased in both groups (between-group difference 55 [–111 to 220], p=0·52); results were similar in the per-protocol population (between-group difference 21 [–214 to 256], p=0.86). In the gastric bypass group, ten of 54 participants had early complications and 17 of 53 had late side-effects. In the sleeve gastrectomy group, eight of 55 participants had early complications and 22 of 54 had late side-effects. No deaths occurred in either group. Interpretation Gastric bypass was found to be superior to sleeve gastrectomy for remission of type 2 diabetes at 1 year after surgery, and the two procedures had a similar beneficial effect on β-cell function. The use of gastric bypass as the preferred bariatric procedure for patients with obesity and type 2 diabetes could improve diabetes care and reduce related societal costs.

Background: Asthma is defined by variable respiratory symptoms and lung function, and may influence work ability. Similarly, obesity may contribute to respiratory symptoms, affect lung function, and reduce work ability. Thus, assessment of the influence of obesity on work ability, respiratory symptoms, and lung function in adults with asthma is needed. Objectives: We hypothesized that patients with obesity and asthma have more respiratory symptoms and reduced work ability and lung function compared with normal-weight patients with asthma. Methods: We examined 626 participants with physician-diagnosed asthma, aged 18–52 years, recruited from a cross-sectional general population study using a comprehensive questionnaire including work ability score, the asthma control test (ACT), height and weight, and spirometry with reversibility testing. Results: Participants with a body mass index (BMI) ≥30 kg/m2 (i.e., obese) had a higher symptom score (OR 1.78, 95% CI 1.14–2.80), current use of asthma medication (1.60, 1.05–2.46), and incidence of ACT scores ≤19 (poor asthma control) (1.81, 1.03–3.18) than participants with BMI ≤24.9 kg/m2 (i.e., normal weight). Post-bronchodilator forced vital capacity (FVC) as a percentage of predicted (β coefficient –4.5) and pre-bronchodilator forced expiratory volume in 1 s as a percentage of predicted (FEV1) (β coefficient –4.6) were negatively associated with BMI ≥30 kg/m2. We found no statistically significant association of BMI >30 kg/m2 (compared to BMI 2) with sick leave (1.21, 0.75–1.70) or reduced work ability (1.23, 0.74–2.04). Conclusions: There were indications that patients with obesity had a higher symptom burden, poorer asthma control, higher consumption of asthma medication, and reduced lung function, in particular for FVC, compared with normal-weight patients.

ObjectiveTo compare the effects of a 2-year camp-based immersion family treatment for obesity with an outpatient family-based treatment for obesity on health-related quality of life (HRQoL) in two generations.DesignRandomised controlled trial.SettingRehabilitation clinic, tertiary care hospital and primary care.PatientsFamilies with at least one child (7–12 years) and one parent, both with obesity.InterventionsSummer camp for 2 weeks, with four repetition weekends, or lifestyle school, including four outpatient days over 4 weeks. Behavioural techniques to promote a healthier lifestyle.Main outcome measuresChildren’s and parents’ HRQoL were assessed using generic and obesity-specific measures. Outcomes were analysed using linear mixed models according to intention to treat, and multiple imputations were used for missing data.ResultsNinety children (50% girls) with a mean (SD) age of 9.7 (1.2) years and body mass index 28.7 (3.9) kg/m2 were included in the analyses. Summer camp children had an estimated mean (95% CI) of 5.3 (0.4 to 10.1) points greater improvement in adiposity-specific HRQoL score at 2 years compared with the lifestyle school children, and this improvement was even larger in the parent proxy-report, where mean difference was 7.3 (95% CI 2.3 to 12.2). Corresponding effect sizes were 0.33 and 0.44. Generic HRQoL questionnaires revealed no significant differences between treatment groups in either children or parents from baseline to 2 years.ConclusionsA 2-year family camp-based immersion obesity treatment programme had significantly larger effects on obesity-specific HRQoL in children’s self-report and parent proxy-reports in children with obesity compared with an outpatient family-based treatment programme.Trial registration numberNCT01110096.

Introduction: Obesity affects a growing proportion of the general population and is prevalent also among subjects with asthma. Studies have demonstrated that both body mass index (BMI) and asthma may impact work ability, but the evidence has been inconclusive. Aims and Objectives: To assess the association between self-reported work ability, and BMI and asthma, and whether there is a synergistic interaction between obesity and asthma on work ability. Methods: Cross-sectional data on self-reported work ability and BMI were obtained in 2013 from 11137 subjects engaged in paid work during the past 12 months, aged 16 to 50 years, from a random sample of the general population of Telemark, Norway. Self-rated work ability was assessed using the Work Ability Score (WAS). Associations between WAS and BMI and by asthma status were examined using multiple logistic regression analysis. Results: The inclusion of the interaction term asthma*BMI in the regression model did not reveal any synergetic effect between asthma and BMI (data not shown). Conclusion: There was a dose-response relationship between reduced work ability and increasing BMI. Asthma was associated with reduced work ability, but there was no indication of a synergetic effect between asthma and obesity in terms of work ability.

Importance The association of bariatric surgery and specialized medical obesity treatment with beneficial and detrimental outcomes remains uncertain. Objective To compare changes in obesity-related comorbidities in patients with severe obesity (body mass index ≥40 or ≥35 and at least 1 comorbidity) undergoing bariatric surgery or specialized medical treatment. Design, Setting, and Participants Cohort study with baseline data of exposures from November 2005 through July 2010 and follow-up data from 2006 until death or through December 2015 at a tertiary care outpatient center, Vestfold Hospital Trust, Norway. Consecutive treatment-seeking adult patients (n = 2109) with severe obesity assessed (221 patients excluded and 1888 patients included). Exposures Bariatric surgery (n = 932, 92% gastric bypass) or specialized medical treatment (n = 956) including individual or group-based lifestyle intervention programs. Main Outcomes and Measures Primary outcomes included remission and new onset of hypertension based on drugs dispensed according to the Norwegian Prescription Database. Prespecified secondary outcomes included changes in comorbidities. Adverse events included complications retrieved from the Norwegian Patient Registry and a local laboratory database. Results Among 1888 patients included in the study, the mean (SD) age was 43.5 (12.3) years (1249 women [66%]; mean [SD] baseline BMI, 44.2 [6.1]; 100% completed follow-up at a median of 6.5 years [range, 0.2-10.1]). Surgically treated patients had a greater likelihood of remission and lesser likelihood for new onset of hypertension (remission: absolute risk [AR], 31.9% vs 12.4%); risk difference [RD], 19.5% [95% CI, 15.8%-23.2%], relative risk [RR], 2.1 [95% CI, 2.0-2.2]; new onset: AR, 3.5% vs 12.2%, RD, 8.7% [95% CI, 6.7%-10.7%], RR, 0.4 [95% CI, 0.3-0.5]; greater likelihood of diabetes remission: AR, 57.5% vs 14.8%; RD, 42.7% [95% CI, 35.8%-49.7%], RR, 3.9 [95% CI, 2.8-5.4]; greater risk of new-onset depression: AR, 8.9% vs 6.5%; RD, 2.4% [95% CI, 1.3%-3.5%], RR, 1.5 [95% CI, 1.4-1.7]; and treatment with opioids: AR, 19.4% vs 15.8%, RD, 3.6% [95% CI, 2.3%-4.9%], RR, 1.3 [95% CI, 1.2-1.4]). Surgical patients had a greater risk for undergoing at least 1 additional gastrointestinal surgical procedure (AR, 31.3% vs 15.5%; RD, 15.8% [95% CI, 13.1%-18.5%]; RR, 2.0 [95% CI, 1.7-2.4]). The proportion of patients with low ferritin levels was significantly greater in the surgical group (26% vs 12%, P Conclusions and Relevance Among patients with severe obesity followed up for a median of 6.5 years, bariatric surgery compared with medical treatment was associated with a clinically important increased risk for complications, as well as lower risks of obesity-related comorbidities. The risk for complications should be considered in the decision-making process.

Aim We analysed the distribution of the body mass index standard deviation scores (BMI-SDS) in children and adolescents seeking treatment for severe obesity, according to the International Obesity Task Force (IOTF), World Health Organization (WHO) and the national Norwegian Bergen Growth Study (BGS) BMI reference charts and the percentage above the International Obesity Task Force 25 cut-off (IOTF-25). Methods This was a cross-sectional study of 396 children aged four to 17 years, who attended a tertiary care obesity centre in Norway from 2009 to 2015. Their BMI was converted to SDS using the three growth references and expressed as the percentage above IOTF-25. The percentage of body fat was assessed by bioelectrical impedance analysis. Results Regardless of which BMI reference chart was used, the BMI-SDS was significantly different between the age groups, with a wider range of higher values up to 10 years of age and a more narrow range of lower values thereafter. The distributions of the percentage above IOTF-25 and percentage of body fat were more consistent across age groups. Conclusions Our findings suggest that it may be more appropriate to use the percentage above a particular BMI cut-off, such as the percentage above IOTF-25, than the IOTF, WHO and BGS BMI-SDS in paediatric patients with severe obesity.

ObjectiveTo compare the effectiveness of a 2-year camp-based family treatment programme and an outpatient programme on obesity in two generations.DesignPragmatic randomised controlled trial.SettingRehabilitation clinic, tertiary care hospital and primary care.PatientsFamilies with at least one child (7–12 years) and one parent with obesity.InterventionsSummer camp for 2 weeks and 4 repetition weekends or lifestyle school including 4 days family education. Behavioural techniques motivating participants to healthier lifestyle.Main outcome measuresChildren: 2-year changes in body mass index (BMI) SD score (SDS). Parents: 2-year change in BMI. Main analyses: linear mixed models.ResultsNinety children (50% girls) were included. Baseline mean (SD) age was 9.7 (1.2) years, BMI 28.7 (3.9) kg/m2 and BMI SDS 3.46 (0.75). The summer-camp children had a lower adjusted estimated mean (95% CI) increase in BMI (−0.8 (−3.5 to −0.2) kg/m2), but the BMI SDS reductions did not differ significantly (−0.11 (−0.49 to 0.05)). The 2-year baseline adjusted BMI and BMI SDS did not differ significantly between summer-camp and lifestyle-school completers, BMI 29.8 (29.1 to 30.6) vs 30.7 (29.8 to 31.6) kg/m2 and BMI SDS 2.96 (2.85 to 3.08) vs 3.11 (2.97 to 3.24), respectively. The summer-camp parents had a small reduction in BMI (−0.9 (−1.8 to −0.03) vs −0.8 (−2.1 to 0.4) in the lifestyle-school group), but the within-group changes did not differ significantly (0.3 (−1.7 to 2.2)).ConclusionsA 2-year family camp-based obesity treatment programme had no significant effect on BMI SDS in children with severe obesity compared with an outpatient family-based treatment programme.Trial registration numberNCT01110096.

Background Rare sequence variants in at least five genes are known to cause monogenic obesity. In this study we aimed to investigate the prevalence of, and characterize, rare coding and splice site variants in LEP , LEPR , MC4R , PCSK1 and POMC in patients with morbid obesity and normal weight controls. Method Targeted next-generation sequencing of all exons in LEP , LEPR , MC4R , PCSK1 and POMC was performed in 485 patients with morbid obesity and 327 normal weight population-based controls from Norway. Results In total 151 variants were detected. Twenty-eight (18.5%) of these were rare, coding or splice variants and five (3.3%) were novel. All individuals, except one control, were heterozygous for the 28 variants, and the distribution of the rare variants showed a significantly higher carrier frequency among cases than controls (9.9% vs. 4.9%, p = 0.011). Four variants in MC4R were classified as pathogenic or likely pathogenic. Conclusion Four cases (0.8%) of monogenic obesity were detected, all due to MC4R variants previously linked to monogenic obesity. Significant differences in carrier frequencies among patients with morbid obesity and normal weight controls suggest an association between heterozygous rare coding variants in these five genes and morbid obesity. However, additional studies in larger cohorts and functional testing of the novel variants identified are required to confirm the findings.

OBJECTIVE FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO influences BMI across adult life span. RESEARCH DESIGN AND METHODS Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmö Diet and Cancer (MDC) and Malmö Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians. RESULTS The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 × 10−8) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 × 10−8). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m2 per risk allele; P = 2.0 × 10−26), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (∆BMI = 0.0 [−0.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults. CONCLUSIONS We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter.

Background Diabetes is classified as Type 1 diabetes, Type 2 diabetes, gestational diabetes and other types. Our goal was to provide an overview of new genetic knowledge of monogenic and type 2 diabetes. Material and method The article is based on literature identified through a non-systematic search in PubMed and own experience concerning research in diabetes genetics and treatment of patients with monogenic diabetes. Results 18 genes have been found for which one single mutation may cause diabetes. The most common causes for such monogenic diabetes are mutations in the genes KCNJ11, ABCC8 and INS when the condition is diagnosed at the age 0 - 6 months, and in the genes HNF1A, GCK, HNF4A and HNF1B when the diagnosis is made later than six months of age. Genetic testing is appropriate in assessment of monogenic diabetes, because antidiabetic tablets rather that insulin injections can be used to treat patients with mutations in certain genes; i.e. KCNJ11, ABCC8, HNF1A and HNF4A. Genome-wide association studies have recently identified about 20 genetic variants that increase the risk of Type 2 diabetes, but which have a low predictive value for development of disease. How these genetic variants can cause Type 2 diabetes has not been assessed and clinical relevance remains to be shown. Interpretation So far, genetic findings only affect diagnosis and treatment of monogenic diabetes.

Lymphangiogenesis is an important event in progression of colorectal cancer (CRC), and the estimated lymphatic vascular density (LVD) probably indicates facilitated lymphatic tumor cell invasion and metastasis. However, at what time point during tumor progression this process is triggered, is unclear. The aim of this study was twofold. Firstly, to examine LVD in paired samples of CRC tissue and normal mucosa with specific emphasis on possible difference in LVD between tumors stages II and III, and secondly, the expression of the lymphangiogenic growth factor fibroblast growth factor-2 (FGF-2). Eighteen patients were studied. Immunostaining for podoplanin was performed to highlight lymphatic vessels. FGF-2 mRNA expression was determined by quantitative real-time RT-PCR, whereas protein expression was quantitatively assessed by densitometric analysis of Western blot signal intensity. The immunoblots were further validated by FGF-2 immunostaining of histological sections. LVD was significantly increased in tumor tissue compared with the normal mucosa but no changes in LVD between stages II and III CRC was observed. FGF-2 was found to be downregulated both at the mRNA and protein level in tumor tissues compared with normal mucosa. Lymphangiogenesis was triggered early in tumor development. An increased LVD was established before the tumor reached stage II. FGF-2 was downregulated in tumor tissue. The importance of this finding remains unclear.

Background Trans fatty acids (TFAs) have been found to impair flow mediated vasodilation and nitric oxide (NO) production. We sought to examine if serum TFA levels are associated with plasma levels of the NO inhibitor asymmetric dimethylarginine (ADMA) and if possible relationships between serum TFA and cardiovascular morbidity or mortality are mediated or modified by plasma ADMA levels. Methods The cohort included patients who underwent coronary angiography for suspected coronary heart disease in 2000–2001. Serum trans 16:1n7 and trans 18:1 isomers were determined by gas liquid chromatography and the summation of these two TFAs is reported as TFA (percentage by weight (wt%) or concentration). Associations between TFAs and ADMA were estimated by calculating the Spearman’s rank correlation coefficient (ρ), and risk associations with AMI, cardiovascular death and all-cause mortality across quartiles of TFAs (wt% or concentration) were explored by Cox modeling. Results A total of 1364 patients (75 % men) with median (25th,75th percentile) age 61 (54, 69) years, serum TFA 0.46 (0.36, 0.56) wt% and plasma ADMA 0.59 (0.50, 0.70) μmol/L were studied. Serum TFA levels (ρ = 0.21, p

Background Nocturnal hypertension, increased night-to-day systolic blood pressure (BP) ratio and nondipper status (night-to-day systolic BP ratio > 0.9) are associated with an increased risk of cardiovascular disease. Our aim was to compare the 1-year effect of Roux-en-Y gastric bypass (RYGB) versus a program of intensive lifestyle intervention (ILI) only on nocturnal hypertension and circadian BP rhythm. Methods The study participants were part of a 1-year, controlled clinical trial comparing the effect of RYGB or ILI on obesity-related comorbidities. Ninety participants (49 in the RYGB group) successfully completed 24-hour ambulatory BP monitoring at baseline and follow-up and were eligible subsequently for analysis. Results A total of 71 subjects (79%) had nocturnal hypertension at baseline. The number of subjects with nocturnal hypertension decreased from 42 to 14 in the RYGB group ( P ≤ .001) and from 29 to 27 ( P = .791) in the ILI group. Subjects in the RYGB group had a lesser adjusted odds ratio (OR) of nocturnal hypertension at follow-up (OR 0.15; 95% confidence interval, 0.05–0.42; P ≤ .001); however, after further adjustment for weight loss, there was no additional beneficial effect of RYGB ( P = .674). No differences between groups regarding improvement in the night-to-day systolic BP ratio were found after adjustment for 24-hour systolic pressure ( P = .107). Both interventions showed a decrease in the proportion of subjects classified as nondippers, namely, 44% ( P ≤ .001) and 28% ( P = .002) in the RYGB and ILI groups, respectively. Conclusion Only RYGB was associated with a decrease in the prevalence of nocturnal hypertension. Both interventions showed an improvement in dipper status, although RYGB was more effective.

OBJECTIVE Mutations in the HNF1A gene are the most common cause of maturity-onset diabetes of the young (MODY). There is a substantial variation in the age at diabetes diagnosis, even within families where diabetes is caused by the same mutation. We investigated the hypothesis that common polygenic variants that predispose to type 2 diabetes might account for the difference in age at diagnosis. RESEARCH DESIGN AND METHODS Fifteen robustly associated type 2 diabetes variants were successfully genotyped in 410 individuals from 203 HNF1A-MODY families, from two study centers in the U.K. and Norway. We assessed their effect on the age at diagnosis both individually and in a combined genetic score by summing the number of type 2 diabetes risk alleles carried by each patient. RESULTS We confirmed the effects of environmental and genetic factors known to modify the age at HNF1A-MODY diagnosis, namely intrauterine hyperglycemia (−5.1 years if present, P = 1.6 × 10−10) and HNF1A mutation position (−5.2 years if at least two isoforms affected, P = 1.8 × 10−2). Additionally, our data showed strong effects of sex (females diagnosed 3.0 years earlier, P = 6.0 × 10−4) and age at study (0.3 years later diagnosis per year increase in age, P = 4.7 × 10−38). There were no strong individual single nucleotide polymorphism effects; however, in the combined genetic score model, each additional risk allele was associated with 0.35 years earlier diabetes diagnosis (P = 5.1 × 10−3). CONCLUSIONS We show that type 2 diabetes risk variants of modest effect sizes reduce the age at diagnosis in HNF1A-MODY. This is one of the first studies to demonstrate that clinical characteristics of a monogenic disease can be modified by common polygenic variants.

Recent genome-wide association studies performed in selected patients and control participants have provided strong support for several new type 2 diabetes susceptibility loci. To get a better estimation of the true risk conferred by these novel loci, we tested a completely unselected population of type 2 diabetes patients from a Norwegian health survey (the HUNT study).We genotyped single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic control participants (the HUNT Study), for all of whom data on BMI, WHR, cholesterol and triacylglycerol levels were available. We used diabetes, measures of obesity and lipid values as phenotypes in case-control and quantitative association study designs.We replicated the association with type 2 diabetes for rs10811661 in the vicinity of CDKN2B (OR 1.20, 95% CI: 1.06-1.37, p=0.004), rs9939609 in FTO (OR 1.14, 95% CI: 1.04-1.25, p=0.006) and rs13266634 in SLC30A8 (OR 1.20, 95% CI: 1.09-1.33, p=3.9 x 10(-4)). We found borderline significant association for the IGFBP2 SNP rs4402960 (OR 1.10, 95% CI: 0.99-1.22). Results for the HHEX SNP (rs1111875) and the CDKAL1 SNP (rs7756992) were non-significant, but the magnitude of effect was similar to previous estimates. We found no support for an association with the less consistently replicated FLJ39370 or PKN2 SNPs. In agreement with previous studies, FTO was most strongly associated with BMI (p=8.4 x 10(-4)).Our data show that SNPs near IGFBP2, CDKAL1, SLC30A8, CDKN2B, HHEX and FTO are also associated with diabetes in non-selected patients with type 2 diabetes.