Jøran Sture Hjelmesæth

• Hjelmesæth, Jøran Sture; Bhat, Suhas; Garvey, W. Timothy; Kolnes, Kristoffer Jensen; Linge, Jennifer & Lingvay, Ildiko [Show all 9 contributors for this article] (2026). Effect of Semaglutide on Thigh Skeletal Muscle Volume, Fat Infiltration and Physical Function in People With Obesity: Secondary Analysis of <scp>STEP UP</scp>. Diabetes, obesity and metabolism. ISSN 1462-8902. doi: 10.1111/dom.71323. Full text in Research Archive Show summary

  ABSTRACT Aims To assess the effect of semaglutide on body composition and physical function. Materials and Methods The phase 3b STEP UP trial randomised adults with body mass index ≥ 30 kg/m 2 to once‐weekly subcutaneous semaglutide 7.2 mg, semaglutide 2.4 mg or placebo for 72 weeks. This prespecified secondary analysis assessed changes in MRI body composition and physical function. Results Of 1407 participants, 55 with a valid baseline scan were included (semaglutide 7.2 mg, n  = 43, 2.4 mg, n  = 6 [pooled semaglutide group, n  = 49]; placebo, n  = 6). Estimated treatment differences (95% confidence intervals; p ‐values) for absolute changes in adipose/muscle compartment volumes for the pooled semaglutide versus placebo group, respectively, were: −11.1 L (−16.5 to −5.7; p  < 0.0001) for adipose body tissue, −1.5 L (−2.9 to −0.1; p  = 0.04) for visceral adipose tissue, −1.7 L (−4.0 to 0.7; p  = 0.16) for lean body tissue, −1.1 L (−2.3 to 0.1; p  = 0.07) for thigh skeletal muscle volume and −0.92%‐points (−1.41 to −0.42; p  = 0.001) for thigh muscle fat infiltration. Similar results were seen for relative changes in adipose/muscle compartment volumes. A sensitivity analysis for the semaglutide 7.2 mg group versus placebo showed similar results. A mean of 13 sit‐to‐stand repetitions in 30 s at baseline, and 15 repetitions at Week 72, was observed in the pooled semaglutide and placebo groups. Conclusions Semaglutide plus lifestyle intervention was associated with reductions in adipose tissue volume, skeletal muscle volume and skeletal muscle fat infiltration, with a preserved number of sit‐to‐stand repetitions. Further research to assess the impact of weight loss on skeletal muscle composition and function should be explored in the future. Trial Registration: ClinicalTrials.gov identifier NCT05646706

• Olsson, Lisa M.; Borgeraas, Heidi; Chakaroun, Rima M.; Hofsø, Dag; Hertel, Jens Kristoffer & Dwibedi, Chinmay [Show all 11 contributors for this article] (2026). Gut microbiota responses to bariatric surgery are associated with metabolic outcomes and type 2 diabetes remission. Nature Metabolism. 8, p. 1212–1228. doi: 10.1038/s42255-026-01525-9. Full text in Research Archive Show summary

  Bariatric surgeries, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), improve obesity and type 2 diabetes (T2D). Both surgeries affect the gut microbiota, but their contribution to T2D remission remains unclear. In this subanalysis (RYGB, n = 39; SG, n = 38) of the randomized controlled Oseberg trial (NCT01778738), in which participants underwent either RYGB or SG surgery, we profiled the faecal microbiome of individuals with obesity and T2D before and 12 months after surgery. We show that both surgeries altered the microbiome in the same direction, but with larger changes after RYGB. The SG-associated altered microbiome composition correlated positively with circulating glucagon-like peptide 1 levels, beta-cell function and 5 year T2D remission. Remission was also linked to increased gene richness and metabolic potential for fermentation, methanogenesis and butyrate production. Notably, these associations persisted after accounting for the extent of weight loss. Our findings indicate that surgery-specific microbial adaptations influence metabolic improvements and may help to explain heterogeneity in T2D remission after bariatric surgery.

• Fardellas, Achilleas; Barreby, Emelie; Brice, Madara; Nock, Sebastian; Russick, Jules & Vankova, Ana [Show all 21 contributors for this article] (2026). ADAR1 Controls Macrophage Scavenging and Lipid‐Buffering Programs in Metabolic Tissues. European Journal of Immunology. ISSN 0014-2980. 56(4). doi: 10.1002/eji.70189. Full text in Research Archive Show summary

  Adenosine deaminase acting on RNA 1 (ADAR1) regulates mRNA fate and function through adenosine‐to‐inosine (A‐to‐I) RNA editing and RNA‐binding activities. While its role in innate immunity is established, the broader regulatory functions of ADAR1 in macrophages remain poorly defined. Here, we systematically profiled ADAR1 expression across human immune cells and identified marked enrichment in macrophages, driven by selective usage of an alternative transcription start site during monocyte‐to‐macrophage differentiation. ADAR1 binds, edits, and modulates key macrophage targets involved in efferocytosis, endocytosis, lysosomal processing, lipid metabolism, and proliferation in an isoform‐specific manner. We further demonstrate that ADAR1 levels and activity are dynamically regulated in adipose tissue and liver during the progression of metabolic disease. Linked to this, macrophage‐specific ablation of ADAR1 co‐cultured in organotypic 3D primary human liver spheroids and exposed to metabolic stress resulted in an exacerbated lipid accumulation phenotype. Finally, we identify a lipid‐associated macrophage‐specific upregulation of ADAR1 in adipose tissue following weight loss interventions, mechanistically driven by free fatty acids. These findings uncover a previously unrecognized role for ADAR1 in lipid‐buffering, scavenging, and proliferative macrophage functions, extending its biological relevance beyond canonical interferon‐mediated immunity and establishing ADAR1 as a key regulator of macrophage adaptation in metabolic disease.

• Salte, Odd Bjørn; Hagen, Rolf Eikeland; Svanevik, Marius; Fagerland, Morten; Risstad, Hilde & Hjelmesæth, Jøran Sture [Show all 9 contributors for this article] (2026). Effect of standard versus long alimentary limb distal Roux-en-Y gastric bypass on weight loss and nutritional outcomes at 10 years in patients with BMI 50–60 kg/m2—a secondary analysis of a randomized clinical trial. British Journal of Surgery. ISSN 0007-1323. 113(1). doi: 10.1093/bjs/znaf285. Full text in Research Archive Show summary

  Abstract Objective Identifying the optimal metabolic bariatric surgery approach for patients with severe obesity with a BMI ≥50 kg/m2 remains challenging. The aim of this long-term follow-up of a randomized clinical trial (RCT) was to compare distal long alimentary limb Roux-en-Y gastric bypass (RYGB) with standard RYGB for 10-year weight loss and nutritional outcomes. Method Secondary analysis of a 10-year follow-up of an RCT with initially 113 patients (BMI 50–60 kg/m2) randomized to either standard (n = 57, 50 cm biliopancreatic/150 cm alimentary limb) or distal long alimentary limb RYGB (n = 56, 50 cm biliopancreatic/150 cm common limb) from March 2011 to April 2013 at two Norwegian hospitals. The final data collection date was 15 August 2023. The primary focus was weight loss (BMI reduction, %total weight loss) and other secondary outcomes included cardiometabolic risk factors, nutritional status, and health-related quality of life (HRQOL). Results Of 113 patients, 79 (69.9%, mean age 50 (s.d. 8.7) years, 50 (63%) females) patients were available for 10-year follow-up (41 standard RYGB, 38 distal RYGB). The 10-year mortality rate was 3.5% (4/113) and all deaths occurred after distal RYGB. One death may have been associated with the surgery in a patient with previously undiagnosed liver cirrhosis at the time of operation. Mean BMI reduction from baseline was 12.0 kg/m2 (95% c.i., 10.8 to 13.2) after standard RYGB and 14.7 kg/m2 (95% c.i., 13.5 to 15.9) after distal RYGB with a between-group difference of 2.7 kg/m2 (95% c.i., 1.0 to 4.5, P = 0.002). The mean percentage total weight loss from baseline was 23.0% (95% c.i., 20.8 to 25.2) after standard RYGB and 28.2% (95% c.i., 26.0 to 30.5) after distal RYGB, with a between-group difference of 5.3% (95% c.i., 2.1 to 8.4, P = 0.001). The distal RYGB group had higher rates of malnutrition (1/57 standard versus 5/56 distal; P = 0.12), diarrhoea (7/57 standard versus 15/56 distal; P = 0.05), and vitamin D deficiency (24/41 standard versus 32/38 distal; P = 0.01). There were no differences between the groups in the prevalence of type 2 diabetes, hypertension, dyslipidaemia, or metabolic syndrome at 10-year follow-up. Four patients underwent revisional surgery due to malnutrition after distal RYGB. There were no statistically significant differences in HRQOL scores between the groups at 10 years (SF-36 physical 44.2 versus 44.1, mental 50.3 versus 47.3; OWLQOL 63 versus 61; all P &gt; 0.2). Conclusions Distal long alimentary limb RYGB resulted in greater weight loss after 10 years with a higher risk of malnutrition, diarrhoea, and vitamin D deficiency. Trial Registration Clinicaltrials.gov NCT00821197

• Ruddox, Vidar; Norum, Ingvild Billehaug; Hjelmesæth, Jøran Sture; Edvardsen, Thor & Otterstad, Jan Erik (2025). The Influence of Gender on Long-Term Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction and the Association with Cardiac Left Ventricular Function. Diagnostics (Basel). 15(22). doi: 10.3390/diagnostics15222901. Full text in Research Archive Show summary

  Background/Objectives: Traditionally, women have been observed to have older age, more co-morbidities, and poorer long-term clinical outcomes following acute myocardial infarction (AMI) when compared to men. However, age-adjusted analyses have demonstrated that gender differences are often attenuated, and the potential influence of left ventricular function and structure have been infrequently studied. The aim of the present study was to evaluate how LV function could influence gender differences in the long-term incidence of a composite of clinically relevant cardiovascular outcomes. Methods: Patients treated with early PCI for AMI were examined with echocardiography 2–4 days after the index AMI and followed by a mean 73 (±13) months. The primary endpoint was the incidence of a composite of total death, recurrent myocardial infarction, hospitalization for angina pectoris with an angiogram documenting progression of coronary artery stenoses, new heart failure, evidence of stroke/transient ischemic attack (TIA), and ventricular arrhythmia. Results: Among the 236 patients studied, 179 (76%) were men, with an average age of 66 (±11) years, and 57 were women (24%), with an age of 65 (±10) years. Men exhibited a higher incidence of anterior STEMI (p = 0.030), lower left ventricular ejection fraction (LVEF) (p = 0.02), reduced global longitudinal strain (p = 0.001), and larger left ventricular end-systolic volume index (LVESVI) (p = 0.007) compared to women. Both genders had similar peak troponin T values and symptom-to-needle times, as well as an equivalent number of stents implanted, prevalence of co-morbidities, and discharge medication. After sixyears of follow-up, Kaplan–Meier curves revealed better long-term cardiovascular outcome-free survival among women (log-rank p = 0.041). Cox regression analysis indicated that neither age nor LVEF influenced this gender difference, which, however, was reduced and became non-significant when LVESVI was added (HR 1.747 (95% CI 0.89–3.43)). No difference in mortality was observed, but men had significantly higher rates of heart failure (p = 0.03). Conclusions: This study demonstrated that men with a previous PCI-treated AMI had a two-fold (HR 2.155) higher risk of a composite long-term cardiovascular outcome as compared with women. The detrimental effect of male gender remained significant after adjustments for age and LVEF, but the male gender effect was reduced and became insignificant after adjustment for age and LVESVI. In view of this, our findings indicate that higher LVESVI may partly explain the detrimental effect of male gender on cardiovascular outcomes after PCI-treated AMI.

• Rønningen, Torunn; Zeng, Yong; Dahl, Mai Britt; Wang, Junbai; Visnovska, Martina & Tannæs, Tone Møller [Show all 18 contributors for this article] (2025). Global mapping of RNA N6-methyladenosine (m6A) in human subcutaneous and visceral adipose tissue reveals novel targets that correlate with clinical variables of obesity. Biomarker Research. 13(1). doi: 10.1186/s40364-025-00857-0. Full text in Research Archive Show summary

  Abstract Background Obesity is a major health challenge and fat accumulation in visceral depots is more strongly associated with metabolic comorbidities than deposition in subcutaneous depots. Epitranscriptomic regulation of gene expression by N 6 -methyladenosine (m 6 A) influences various aspects of RNA metabolism, however the m 6 A methylome in human adipose tissue and its relationship with fat distribution has not yet been investigated in detail. Methods In this study, we performed epitranscriptomic mapping of m 6 A in intra-individually paired samples of subcutaneous (SAT) and omental visceral adipose tissue (OVAT) from women with normal weight (BMI ≤25, n  = 3) and obesity (BMI ≥35, n  = 10) using meRIP-seq (discovery cohort). We further investigated differential m 6 A methylation for specific target genes in a larger cohort of individuals with obesity ( n  = 72, validation cohort) using meRIP-qPCR. meRIP-seq was performed for primary adipocytes from a subset of the patients ( n  = 4) to account for cell type specific differences. Results We here provide the first global map of m 6 A in human adipose tissue in paired samples of SAT and OVAT. We show an overall high overlap in m 6 A sites between individuals and depots, but also distinct depot-specific differences. We identify 339 target genes showing depot-specific m 6 A methylation. Depot-specific methylation was validated for selected sites in SEMA3A , SNAP47 and PPP1R9A in a larger validation cohort. We additionally identify differentially methylated targets between lean individuals and individuals with obesity, including TSC22D1 , FMNL2 and IL1R1 . By combining data from primary adipocytes with data from corresponding bulk adipose tissue, we identified a higher number of genes containing m 6 A in non-adipocyte cells in OVAT compared to SAT. Mechanistically, we show for selected targets that m 6 A affects RNA lifetime in pre-adipocyte cell culture models. Importantly, m 6 A methylation in selected targets correlates with clinically important variables related to obesity, fat distribution and glucose metabolism. Conclusions We identify a catalogue of novel targets showing adipose tissue depot specific m 6 A methylation, with potential as biomarkers in metabolic disease. Our findings underscore the regulatory role of m 6 A in obesity and provide valuable insights for future research. The datasets generated represent a significant resource for further insight in adipose tissue biology and its implications for metabolic health.

• Deanfield, John; Lincoff, A Michael; Kahn, Steven E; Emerson, Scott S; Lingvay, Ildiko & Scirica, Benjamin M [Show all 21 contributors for this article] (2025). Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial. The Lancet. ISSN 0140-6736. doi: 10.1016/s0140-6736(25)01375-3. Full text in Research Archive Show summary

  Background: The SELECT trial found semaglutide reduced major adverse cardiovascular events (MACE) in patients with overweight or obesity with cardiovascular disease but without diabetes. We report a prespecified analysis of the SELECT trial on the relationships between baseline adiposity measures, treatment-induced adiposity changes, and subsequent MACE risk. Methods: Patients aged at least 45 years, with a BMI of at least 27 kg/m2 were enrolled in 41 countries (804 sites) and randomised 1:1 to once-weekly semaglutide 2·4 mg or placebo. The primary outcome was time to first MACE (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke). Adiposity measures included weight and waist circumference. In this analysis, risk of MACE occurring after 20 weeks was assessed between patients by adiposity changes in the first 20 weeks and, in a separate analysis, all in-trial MACE were assessed between patients by adiposity changes over 104 weeks. This trial is registered with ClinicalTrials.gov, NCT03574597. Findings: Semaglutide significantly reduced MACE incidence compared with placebo among 17 604 patients enrolled in SELECT, with consistent benefits across all baseline weight and waist circumference categories. In the semaglutide group, analyses for linear trends showed lower baseline bodyweight and waist circumference were associated with lower incidence of MACE-an average 4% reduction in risk per 5 kg lower bodyweight (hazard ratio [HR] 0·96 [95% CI 0·94-0·99]; p=0·001) and per 5 cm smaller waist circumference (0·96 [0·93-0·99]; p=0·004). In the placebo group, lower baseline waist circumference (0·96 [0·94-0·99]; p=0·007), but not bodyweight (0·99 [0·97-1·01]; p=0·28), was associated with a lower MACE risk and weight loss was paradoxically associated with increased MACE risk. In those receiving semaglutide there was no linear trend linking weight loss at week 20 to subsequent MACE risk, but greater waist circumference reduction at week 20 was associated with lower subsequent MACE risk, and waist circumference reduction by week 104 was associated with lower in-trial risk of MACE. An estimated 33% of the observed benefit on MACE was mediated through waist circumference reduction (HR 0·86 [95% CI 0·77-0·97] after adjustment for time-varying changes in waist circumference). Interpretation: The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction.

• Wharton, Sean; Freitas, Paula; Hjelmesæth, Jøran Sture; Kabisch, Maria; Kandler, Kristian & Lingvay, Ildiko [Show all 9 contributors for this article] (2025). Once-weekly semaglutide 7·2 mg in adults with obesity (STEP UP): a randomised, controlled, phase 3b trial. The Lancet Diabetes and Endocrinology. ISSN 2213-8587. 13(11), p. 949–963. doi: 10.1016/s2213-8587(25)00226-8. Full text in Research Archive Show summary

  Background: Once-weekly subcutaneous semaglutide 2·4 mg is approved for weight management in people with obesity and related complications; however, some individuals do not reach their therapeutic goals with this dose. We aimed to test the efficacy and safety of a higher dose of semaglutide (7·2 mg) in people with obesity. Methods: STEP UP was a phase 3b, randomised, double-blind, placebo-controlled and active-controlled trial conducted across 95 hospitals, specialist clinics, and medical centres in 11 countries in adults with BMI 30 kg/m2 or greater, without diabetes. Participants were randomly assigned (5:1:1) to receive once-weekly subcutaneous semaglutide 7·2 mg, 2·4 mg, or placebo, with a lifestyle intervention, for 72 weeks. Coprimary endpoints were percentage change in bodyweight and the proportion of participants with a bodyweight reduction of 5% or greater for semaglutide 7·2 mg versus placebo from baseline to week 72 (treatment policy estimand). Confirmatory secondary endpoints were percentage change in bodyweight with 7·2 mg versus 2·4 mg, change in waist circumference (cm), and proportion of participants with bodyweight reductions of 10% or greater, 15% or greater, 20% or greater, and 25% or greater versus placebo, and 20% or greater and 25% or greater versus 2·4 mg. Safety was assessed in all participants who received at least one dose of the trial product. This trial is registered with ClinicalTrials.gov (NCT05646706) and is now completed. Findings: Between Jan 1, 2023, and Nov 26, 2024, 1407 participants were randomly assigned to semaglutide 7·2 mg (n=1005), semaglutide 2·4 mg (n=201), or placebo (n=201). 1037 (73·7%) of 1407 participants were female, the mean age was 47 (SD 12) years, mean bodyweight was 113·0 (24·1) kg, and mean BMI was 39·9 (7·1) kg/m2. The mean change in bodyweight was greater with semaglutide 7·2 mg versus 2·4 mg (-18·7% [SE 0·4] vs -15·6% [0·7]; estimated treatment difference [ETD] -3·1% [95% CI -4·7 to -1·6]; p<0·0001) and with semaglutide 7·2 mg versus placebo (-18·7% [0·4] vs -3·9% [0·6]; -14·8% [-16·2 to -13·4]; p<0·0001). Participants in the semaglutide 7·2 mg group were more likely than those in the placebo group to reach bodyweight reductions of 5% or greater (odds ratio 12·1 [95% CI 8·3 to 17·6]; p<0·0001), 10% or greater (14·5 [9·6 to 21·9]; p<0·0001), 15% or greater (20·3 [11·2 to 36·8]; p<0·0001), 20% or greater (27·3 [10·9 to 68·0]; p<0·0001), and 25% or greater (127·4 [36·8 to 441·4]; p<0·0001); and more likely than those in the 2·4 mg group to reach bodyweight reductions of 20% or greater (1·8 [1·3 to 2·4]; p=0·0006) and 25% or greater (2·4 [1·6 to 3·5]; p<0·0001). Improvements in waist circumference were observed with semaglutide 7·2 mg versus placebo (ETD -11·7 cm [95% CI -13·0 to -10·4]; p<0·0001). Gastrointestinal adverse events were more common with semaglutide 7·2 mg (711 [70·8%] of 1004) versus 2·4 mg (123 [61·2%] of 201) or placebo (86 [42·8%] of 201), as was dysaesthesia (230 [22·9%], 12 [6·0%], and one [0·5%], respectively). Serious adverse events were reported by 68 (6·8%) of 1004 participants with semaglutide 7·2 mg, 22 (10·9%) of 201 with semaglutide 2·4 mg, and 11 (5·5%) of 201 with placebo. Interpretation: Semaglutide 7·2 mg was superior to placebo and 2·4 mg for bodyweight reduction in adults with obesity, while retaining a favourable risk-benefit profile.

• Gopalakrishnan, Vancheswaran; Kumar, Chanchal; Robertsen, Ida; Morehouse, Christopher; Sparklin, Ben & Khader, Shameer [Show all 19 contributors for this article] (2025). A multi-omics microbiome signature is associated with the benefits of gastric bypass surgery and is differentiated from diet induced weight loss through 2 years of follow-up. Mucosal Immunology. ISSN 1933-0219. 18(4), p. 825–835. doi: 10.1016/j.mucimm.2025.04.002. Full text in Research Archive Show summary

  Roux-en-Y gastric bypass (GBP) surgery is an effective treatment for reducing body weight and correcting metabolic dysfunction in individuals with severe obesity. Herein, we characterize the differences between very low energy diet (VLED) and GBP induced weight loss by multi-omic analyses of microbiome and host features in a non-randomized, controlled, single-center study. Eighty-eight participants with severe obesity were recruited into two arms – GBP versus VLED with matching weight loss for 6 weeks and 2-years of follow-up. A dramatic shift in the distribution of gut microbial taxa and their functional capacity was seen in the GBP group at Week 2 after surgery and was sustained through 2 years. Multi-omic analyses were performed after 6 weeks of matching weight loss between the GBP and VLED groups, which pointed to microbiome derived metabolites such as indoxyl sulphate as characterizing the GBP group. We also identified an inverse association between Streptococcus parasanguinis (an oral commensal) and plasma levels of tryptophan and tyrosine. These data have important implications, as they reveal a significant robust restructuring of the microbiome away from a baseline dysbiotic state in the GBP group. Furthermore, multi-omics modelling points to potentially novel mechanistic insights at the intersection of the microbiome and host.

• Hauge, Jostein Wågen; Borgeraas, Heidi; Birkeland, Kåre Inge; Johnson, Line Kristin; Hertel, Jens Kristoffer & Hagen, Milada [Show all 16 contributors for this article] (2025). Effect of gastric bypass versus sleeve gastrectomy on the remission of type 2 diabetes, weight loss, and cardiovascular risk factors at 5 years (Oseberg): secondary outcomes of a single-centre, triple-blind, randomised controlled trial. The Lancet Diabetes and Endocrinology. ISSN 2213-8587. 13(5), p. 397–409. doi: 10.1016/S2213-8587(24)00396-6. Full text in Research Archive
• Saeed, Sadia; Poulsen, Lars La Cour; Visnovska, Martina; Hoffmann, Anne; Ghosh, Adhideb & Wolfrum, Christian [Show all 18 contributors for this article] (2025). Chromatin landscape in paired human visceral and subcutaneous adipose tissue and its impact on clinical variables in obesity. EBioMedicine. 114. doi: 10.1016/j.ebiom.2025.105653. Full text in Research Archive Show summary

  Background Obesity is a global health challenge and adipose tissue exhibits distinct depot-specific characteristics impacting differentially on the risk of metabolic comorbidities. Methods Here, we integrate chromatin accessibility (ATAC-seq) and gene expression (RNA-seq) data from intra-individually paired human subcutaneous (SAT) and omental visceral adipose tissue (OVAT) samples to unveil depot-specific regulatory mechanisms. Findings We identified twice as many depot-specific differentially accessible regions (DARs) in OVAT compared to SAT. SAT-specific regions showed enrichment for adipose tissue enhancers involving genes controlling extracellular matrix organization and metabolic processes. In contrast, OVAT-specific regions showed enrichment in promoters linked to genes associated with cardiomyopathies. Moreover, OVAT-specific regions were enriched for bivalent transcription start site and repressive chromatin states, suggesting a “lingering” regulatory state. Motif analysis identified CTCF and BACH1 as most significantly enriched motifs in SAT and OVAT-specific DARs, respectively. Distinct gene sets correlated with important clinical variables of obesity, fat distribution measures, as well as insulin, glucose, and lipid metabolism. Interpretation We provide an integrated analysis of chromatin accessibility and transcriptional profiles in paired human SAT and OVAT samples, offering new insights into the regulatory landscape of adipose tissue and highlighting depot-specific mechanisms in obesity pathogenesis.

• Kushner, Robert F.; Ryan, Donna H.; Deanfield, John; Kokkinos, Alexander; Cercato, Cintia & Wilding, John P. [Show all 18 contributors for this article] (2025). Safety profile of semaglutide versus placebo in the SELECT study: a randomized controlled trial. Obesity. ISSN 1930-7381. 33(3), p. 452–462. doi: 10.1002/oby.24222. Full text in Research Archive
• Otterstad, Jan Erik; Munkhaugen, John; Ruddox, Vidar; Edvardsen, Thor & Hjelmesæth, Jøran Sture (2024). Association of normal body mass index and weight loss with long-term major cardiovascular events after PCI for myocardial infarction. Scandinavian Cardiovascular Journal. ISSN 1401-7431. 58(1). doi: 10.1080/14017431.2024.2386984. Full text in Research Archive Show summary

  Objectives: To investigate whether normal body mass index (BMI) shortly after percutaneous coronary intervention (PCI) for myocardial infarction is associated with increased risk of long-term major cardiovascular events (MACE), and to explore potential clinical determinants of long-term weight loss (WL) after PCI. Methods: Single-center cohort study with 5-year follow-up of patients treated with PCI for myocardial infarction between 2016 and 2018. Categorical WL was defined as > 0 kg body weight reduction from baseline to end of follow-up. Results: Of 236 patients (24% women), mean age was 64.9 ± 10.2 years and mean BMI within 4 days after PCI was 27.1 ± 4.3 kg/m2. Seventy-five patients (32%) had at least one MACE, equally distributed between those with normal weight (31%), overweight (32%), and obesity (31%). Patients with overweight or obesity had a lower crude mortality rate than their normal weight counterparts (7.4% vs 16.4%, p = 0.049), but the relative hazard of death did not differ from those with normal weight, HR 0.50, 95% CI 0.22-1.15. Patients with either a long-term WL (n = 112) or no WL (n = 95) had a comparable incidence of non-fatal MACE (27% vs 22%, p = 0.518). The proportion of patients reporting unintentional weight loss was significantly higher in the normal weight group (82%) compared with those with overweight (41%) or obesity (28%), p < 0.001. Conclusion: Our results did not confirm any association between normal BMI after PCI and long-term MACE. However, patients with normal BMI at baseline had a higher incidence of unintentional WL than those with elevated BMI. Trial registration: Current research information system in Norway (CRISTIN): ID 542528

• Wahlström, Annika; Aydin, Ömrüm; Olsson, Lisa M.; Sjöland, Wilhelm; Henricsson, Marcus & Lundqvist, Annika [Show all 16 contributors for this article] (2024). Alterations in bile acid kinetics after bariatric surgery in patients with obesity with or without type 2 diabetes. EBioMedicine. 106. doi: 10.1016/j.ebiom.2024.105265. Full text in Research Archive Show summary

  Background: Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking. Methods: In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort. Findings: We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort. Interpretation: Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission.

• Karlsson, Cecilia; Johnsen, Line Kristin; Greasley, Peter; Retterstøl, Kjetil; Hedberg, Jonatan & Hall, Martin [Show all 18 contributors for this article] (2024). Gastric Bypass vs Diet and Cardiovascular Risk Factors: A Nonrandomized Controlled Trial. JAMA Surgery. ISSN 2168-6254. 159(9), p. 971–980. doi: 10.1001/jamasurg.2024.2162. Full text in Research Archive Show summary

  Importance Roux-en-Y gastric bypass (RYGB) is associated with reduced cardiovascular (CV) risk factors, morbidity, and mortality. Whether these effects are specifically induced by the surgical procedure or the weight loss is unclear. Objective To compare 6-week changes in CV risk factors in patients with obesity undergoing matching caloric restriction and weight loss by RYGB or a very low-energy diet (VLED). Design, Setting, and Participants This nonrandomized controlled study (Impact of Body Weight, Low Calorie Diet, and Gastric Bypass on Drug Bioavailability, Cardiovascular Risk Factors, and Metabolic Biomarkers [COCKTAIL]) was conducted at a tertiary care obesity center in Norway. Participants were individuals with severe obesity preparing for RYGB or a VLED. Recruitment began February 26, 2015; the first patient visit was on March 18, 2015, and the last patient visit (9-week follow-up) was on August 9, 2017. Data were analyzed from April 30, 2021, through June 29, 2023. Interventions VLED alone for 6 weeks or VLED for 6 weeks after RYGB; both interventions were preceded by 3-week LED. Main Outcomes and Measures Between-group comparisons of 6-week changes in CV risk factors. Results Among 78 patients included in the analyses, the mean (SD) age was 47.5 (9.7) years; 51 (65%) were women, and 27 (35%) were men. Except for a slightly higher mean (SD) body mass index of 44.5 (6.2) in the RYGB group (n = 41) vs 41.9 (5.4) in the VLED group (n = 37), baseline demographic and clinical characteristics were similar between groups. Major atherogenic blood lipids (low-density lipoprotein cholesterol, non–high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein[a]) were reduced after RYGB in comparison with VLED despite a similar fat mass loss. Mean between-group differences were −17.7 mg/dL (95% CI, −27.9 to −7.5), −17.4 mg/dL (95% CI, −29.8 to −5.0) mg/dL, −9.94 mg/dL (95% CI, −15.75 to −4.14), and geometric mean ratio was 0.55 U/L (95% CI, 0.42 to 0.72), respectively. Changes in glycemic control and blood pressure were similar between groups. Conclusions and Relevance This study found that clinically meaningful reductions in major atherogenic blood lipids were demonstrated after RYGB, indicating that RYGB may reduce CV risk independent of weight loss. Trial Registration ClinicalTrials.gov Identifier: NCT02386917

• Asbjørnsen, Rikke Aune; Børøsund, Elin; Hjelmesæth, Jøran Sture; Smedsrød, Mirjam Lien; Ollivier, Marianne & Wentzel, Jobke [Show all 9 contributors for this article] (2024). Digital behaviour change intervention for weight loss maintenance in adults with obesity: a feasibility pilot study of eCHANGE. Behaviour and Information Technology. ISSN 0144-929X. p. 1–19. doi: 10.1080/0144929X.2024.2399299. Full text in Research Archive Show summary

  Successful weight maintenance after weight loss is challenging. Digital interventions may facilitate behaviour change to prevent weight regain, however little is known about the acceptance and use of digital interventions in support of weight maintenance. This mixed methods study aims to evaluate user experiences, system use, and preliminary efficacy of eCHANGE, an application based self-management intervention for weight loss maintenance. A 3-month multi-site single group feasibility pilot study was conducted among adults (N = 60) with BMI ≥30 kg/m2, aiming to maintain weight after weight loss of ≥8%. User experiences and system use were examined through validated questionnaires, system use log data, and individual interviews (n = 15). Preliminary efficacy testing included body weight and patient reported outcome measures. Participants rated eCHANGE usability and usefulness as good in support of weight maintenance, with variation in usage. Analysis indicated that higher behavioural engagement scores were statistically significantly associated with frequency of technology usage. Weight loss was maintained by 83% of the participants at 3-months (i.e. defined as weight change of <3% of baseline body weight (kg)). Digital interventions, combining persuasive system design principles and behaviour change techniques, supporting self-regulation and maintenance of health behaviours, have the potential to facilitate weight maintenance after weight loss.

• Kvitne, Kine Eide; Hjelmesæth, Jøran Sture; Hovd, Markus; Sandbu, Rune; Johnson, Line Kristin & Andersson, Shalini [Show all 11 contributors for this article] (2024). Oral Drug Dosing After Gastric Bypass and Diet-Induced Weight Loss: Simpler Than We Think? Lessons Learned From the COCKTAIL Study. Clinical Pharmacology and Therapeutics. ISSN 0009-9236. 16(3), p. 647–652. doi: 10.1002/cpt.3307. Full text in Research Archive Show summary

  This article summarizes the lessons learned from the COCKTAIL study: an open, three-armed, single-center study including patients with obesity scheduled for treatment with Roux-en-Y gastric bypass (RYGB) or nonsurgical calorie restriction, and a normal- to overweight control group. The clinical implications of the results from multiple peer-reviewed articles describing the effects of RYGB, severe caloric restriction, weight loss, and type 2 diabetes on the in vivo activity and protein expression of drug-metabolizing enzymes (cytochrome P450 (CYP) 1A2, 2C9, 2C19, and 3A) and transporters (DMETs; organic anion-transporting polypeptide (OATP) 1B1 and P-glycoprotein (P-gp)) are discussed in the perspective of three clinically relevant questions: (1) How should clinicians get the dose right in patients after RYGB? (2) Will drug disposition in patients with obesity be normalized after successful weight loss? (3) Are dose adjustments needed according to obesity and diabetes status? Overall, RYGB seems to have a lower impact on drug disposition than previously assumed, but clinicians should pay close attention to drugs with a narrow therapeutic range or where a high maximum drug concentration may be problematic. Whether obesity-related alterations of DMETs normalize with substantial weight loss depends on the DMET in question. Obesity and diabetes downregulate the in vivo activity of CYP2C19 and CYP3A (only obesity) but whether substrate drugs should be dose adjusted is also dependent on other factors that influence clearance, that is, liver blood flow and protein binding. Finally, we recommend frequent and individualized follow-up due to high inter- and intraindividual variability in these patients, particularly following RYGB.

• Bliddal, Henning; Bays, Harold; Czernichow, Sébastien; Hemmingsson, Joanna Uddén; Hjelmesæth, Jøran Sture & Morville, Thomas Hoffmann [Show all 12 contributors for this article] (2024). Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. New England Journal of Medicine. ISSN 0028-4793. 391(17), p. 1573–1583. doi: 10.1056/NEJMoa2403664. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Hjelmesæth, Jøran Sture; Smedsrød, Mirjam Lien; Wentzel, Jobke; Clarke, Matthew & Kelders, Saskia M. [Show all 8 contributors for this article] (2024). Implementation of a Digital Behavior Change Intervention (eCHANGE) for Weight Loss Maintenance Support: A Service Design and Technology Transfer Approach. Frontiers in Digital Health. 6. doi: 10.3389/fdgth.2024.1394599. Full text in Research Archive Show summary

  Obesity is a chronic disease, and while weight loss is achievable, long-term weight loss maintenance is difficult and relapse common for people living with obesity. Aiming to meet the need for innovative approaches, digital behavior change interventions show promise in supporting health behavior change to maintain weight after initial weight loss. Implementation of such interventions should however be part of the design and development processes from project initiation to facilitate uptake and impact. Based on the development and implementation process of eCHANGE, an evidence-informed application-based self-management intervention for weight loss maintenance, this manuscript provides suggestions and guidance into; (1) How a service design approach can be used from initiation to implementation of digital interventions, and (2) How a technology transfer process can accelerate implementation of research-based innovation from idea to market.

• Tønnesen, Christer Julseth; Hjelmesæth, Jøran Sture; Aabakken, Lars; Lund, Randi Størdal; Johnson, Line Kristin & Hertel, Jens Kristoffer [Show all 9 contributors for this article] (2023). A pilot study of implementation of endoscopic sleeve gastroplasty (ESG) in Norway. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 58(10), p. 1180–1184. doi: 10.1080/00365521.2023.2204389. Full text in Research Archive Show summary

  Bariatric surgery is the most effective treatment for obesity but is invasive and associated with serious complications. Endoscopic sleeve gastroplasty (ESG) is a less invasive weight loss procedure to reduce the stomach volume by full-thickness sutures. ESG has been adopted in many countries, but implementation at Scandinavian centres has not yet been documented. We performed a clinical pilot trial at a Norwegian centre with the primary objective to assess the feasibility of the ESG procedure. Patients and methods We included the first 10 patients treated with ESG at a Norwegian centre in a single-arm pilot study. The eligibility criteria were either a body mass index (BMI) of 40–49.9 kg/m2, BMI 35–39.9 kg/m2 and at least one obesity-related comorbidity, or BMI 30–34.9 kg/m2 and type 2 diabetes. Patient follow-up resembled the scheme used for bariatric surgery at the center, including dietary plans and outpatient visits. Results All procedures were technically successful except for one patient who had adhesions between the stomach and anterior abdominal wall, related to a prior hernia repair, resulting in less-than-intended stomach volume reduction. Mean total body weight loss (TBWL) after 26 and 52 weeks was 12.2% (95% CI 8.1–16.2) and 9.1% (95% CI 3.3 − 15.0). One patient experienced a minor suture-induced diaphragmatic injury, which was successfully managed conservatively. Conclusions This first Scandinavian clinical trial of ESG, documenting the implementation of the procedure at a Norwegian center, demonstrated acceptable feasibility and safety, with large variations in individual weight loss during the 52-week follow-up period.

• Hovd, Markus Herberg; Robertsen, Ida; Johnson, Line Kristin; Krogstad, Veronica; Wegler, Christine & Kvitne, Kine Eide [Show all 16 contributors for this article] (2023). Neither Gastric Bypass Surgery Nor Diet-Induced Weight-Loss Affect OATP1B1 Activity as Measured by Rosuvastatin Oral Clearance. Clinical Pharmacokinetics. ISSN 0312-5963. 62(5), p. 725–735. doi: 10.1007/s40262-023-01235-5. Full text in Research Archive Show summary

  Introduction Rosuvastatin pharmacokinetics is mainly dependent on the activity of hepatic uptake transporter OATP1B1. In this study, we aimed to investigate and disentangle the effect of Roux-en-Y gastric bypass (RYGB) and weight loss on oral clearance (CL/F) of rosuvastatin as a measure of OATP1B1-activity. Methods Patients with severe obesity preparing for RYGB (n = 40) or diet-induced weight loss (n = 40) were included and followed for 2 years, with four 24-hour pharmacokinetic investigations. Both groups underwent a 3-week low-energy diet (LED; < 1200 kcal/day), followed by RYGB or a 6-week very-low-energy diet (VLED; < 800 kcal/day). Results A total of 80 patients were included in the RYGB group (40 patients) and diet-group (40 patients). The weight loss was similar between the groups following LED and RYGB. The LED induced a similar (mean [95% CI]) decrease in CL/F in both intervention groups (RYGB: 16% [0, 31], diet: 23% [8, 38]), but neither induced VLED resulted in any further changes in CL/F. At Year 2, CL/F had increased by 21% from baseline in the RYGB group, while it was unaltered in the diet group. Patients expressing the reduced function SLCO1B1 variants (c.521TC/CC) showed similar changes in CL/F over time compared with patients expressing the wild-type variant. Conclusions Neither body weight, weight loss nor RYGB per se seem to affect OATP1B1 activity to a clinically relevant degree. Overall, the observed changes in rosuvastatin pharmacokinetics were minor, and unlikely to be of clinical relevance.

• Handin, Niklas; Yuan, Di; Ölander, Magnus; Wegler, Christine; Karlsson, Cecilia & Jansson-Löfmark, Rasmus [Show all 10 contributors for this article] (2023). Proteome deconvolution of liver biopsies reveals hepatic cell composition as an important marker of fibrosis. Computational and Structural Biotechnology Journal. 21, p. 4361–4369. doi: 10.1016/j.csbj.2023.08.037. Full text in Research Archive Show summary

  Human liver tissue is composed of heterogeneous mixtures of different cell types and their cellular stoichiometry can provide information on hepatic physiology and disease progression. Deconvolution algorithms for the identification of cell types and their proportions have recently been developed for transcriptomic data. However, no method for the deconvolution of bulk proteomics data has been presented to date. Here, we show that proteomes, which usually contain less data than transcriptomes, can provide useful information for cell type deconvolution using different algorithms. We demonstrate that proteomes from defined mixtures of cell lines, isolated primary liver cells, and human liver biopsies can be deconvoluted with high accuracy. In contrast to transcriptome-based deconvolution, liver tissue proteomes also provided information about extracellular compartments. Using deconvolution of proteomics data from liver biopsies of 56 patients undergoing Roux-en-Y gastric bypass surgery we show that proportions of immune and stellate cells correlate with inflammatory markers and altered composition of extracellular matrix proteins characteristic of early-stage fibrosis. Our results thus demonstrate that proteome deconvolution can be used as a molecular microscope for investigations of the composition of cell types, extracellular compartments, and for exploring cell-type specific pathological events. We anticipate that these findings will allow the refinement of retrospective analyses of the growing number of proteome datasets from various liver disease states and pave the way for AI-supported clinical and preclinical diagnostics.

• Svanevik, Marius; Lorentzen, Jolanta Halabowska; Borgeraas, Heidi; Sandbu, Rune; Seip, Birgitte Karen Berggreen & Medhus, Asle Wilhelm [Show all 11 contributors for this article] (2023). Patient-reported outcomes, weight loss, and remission of type 2 diabetes 3 years after gastric bypass and sleeve gastrectomy (Oseberg); a single-centre, randomised controlled trial. The Lancet Diabetes and Endocrinology. ISSN 2213-8587. 11(8), p. 555–566. doi: 10.1016/S2213-8587(23)00127-4. Full text in Research Archive Show summary

  Little is known about the comparative effects of various bariatric procedures on patient-reported outcomes. We aimed to compare 3-year effects of gastric bypass and sleeve gastrectomy on patient-reported outcome measures in patients with obesity and type 2 diabetes. Methods The Oseberg trial was a single-centre, parallel-group, randomised trial at Vestfold Hospital Trust, a public tertiary obesity centre in Tønsberg, Norway. Eligible patients were aged 18 years or older with previously verified BMI 35·0 kg/m 2 or greater. Diabetes was diagnosed if glycated haemoglobin was at least 6·5% (48 mmol/mol) or by their use of anti-diabetic medications with glycated haemoglobin at least 6·1% (43 mmol/mol). Eligible patients were randomly assigned (1:1) to gastric bypass or sleeve gastrectomy. All patients received identical preoperative and postoperative treatment. Randomisation was done with a computerised random number generator and a block size of ten. Study personnel, patients, and the primary outcome assessor were blinded to allocations for 1 year. The prespecified secondary outcomes reported here were 3-year changes in several clinically important patient-reported outcomes, weight loss, and diabetes remission. Analyses were done in the intention to treat population. This trial is ongoing, closed to recruitment and is registered with ClinicalTrials.gov , NCT01778738 . Findings Between Oct 15, 2012 and Sept 1, 2017, 319 consecutive patients with type 2 diabetes scheduled for bariatric surgery were assessed for eligibility. 101 patients were not eligible (29 did not have type 2 diabetes according to inclusion criteria and 72 other exclusion criteria) and 93 declined to participate. 109 patients were enrolled and randomly assigned to sleeve gastrectomy (n=55) or gastric bypass (n=54). 72 (66%) of 109 patients were female and 37 (34%) were male. 104 (95%) of patients were White. 16 patients were lost to follow up and 93 (85%) patients completed the 3-year follow-up. Three additional patients were contacted by phone for registration of comorbidities Compared with sleeve gastrectomy, gastric bypass was associated with a greater improvement in weight-related quality of life (between group difference 9·4, 95% CI 3·3 to 15·5), less reflux symptoms (0·54, 0·17 to –0·90), greater total bodyweight loss (8% difference, 25% vs 17%), and a higher probability of diabetes remission (67% vs 33%, risk ratio 2·00; 95% CI 1·27 to 3·14). Five patients reported postprandial hypoglycaemia in the third year after gastric bypass versus none after sleeve-gastrectomy (p=0·059). Symptoms of abdominal pain, indigestion, diarrhoea, dumping syndrome, depression, binge eating, and appetitive drive did not differ between groups. Interpretation At 3 years, gastric bypass was superior to sleeve gastrectomy in patients with type 2 diabetes and obesity regarding weight related quality of life, reflux symptoms, weight loss, and remission of diabetes, while symptoms of abdominal pain, indigestion, diarrhoea, dumping, depression and binge eating did not differ between groups. This new patient-reported knowledge can be used in the shared decision-making process to inform patients about similarities and differences between expected outcomes after the two surgical procedures.

• Kvitne, Kine Eide; Hovd, Markus; Johnsen, Line Kristin; Wegler, Christine; Karlsson, Cecilia & Artursson, Per [Show all 14 contributors for this article] (2023). Digoxin Pharmacokinetics in Patients with Obesity Before and After a Gastric Bypass or a Strict Diet Compared with Normal Weight Individuals. Clinical Pharmacokinetics. ISSN 0312-5963. 63(1), p. 103–120. doi: 10.1007/s40262-023-01320-9. Full text in Research Archive Show summary

  Background and Objective Several drugs on the market are substrates for P-glycoprotein (P-gp), an efflux transporter highly expressed in barrier tissues such as the intestine. Body weight, weight loss, and a Roux-en-Y gastric bypass (RYGB) may influence P-gp expression and activity, leading to variability in the drug response. The objective of this study was therefore to investigate digoxin pharmacokinetics as a measure of the P-gp phenotype in patients with obesity before and after weight loss induced by an RYGB or a strict diet and in normal weight individuals. Methods This study included patients with severe obesity preparing for an RYGB (n = 40) or diet-induced weight loss (n = 40) and mainly normal weight individuals scheduled for a cholecystectomy (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day) followed by an additional 6 weeks of <800 kcal/day induced by an RYGB (performed at week 3) or a very-low-energy diet. Follow-up time was 2 years, with four digoxin pharmacokinetic investigations at weeks 0, 3, and 9, and year 2. Hepatic and jejunal P-gp levels were determined in biopsies obtained from the patients undergoing surgery. Results The RYGB group and the diet group had a comparable weight loss in the first 9 weeks (13 ± 2.3% and 11 ± 3.6%, respectively). During this period, we observed a minor increase (16%) in the digoxin area under the concentration–time curve from zero to infinity in both groups: RYGB: 2.7 µg h/L [95% confidence interval (CI) 0.67, 4.7], diet: 2.5 µg h/L [95% CI 0.49, 4.4]. In the RYGB group, we also observed that the time to reach maximum concentration decreased after surgery: from 1.0 ± 0.33 hours at week 3 to 0.77 ± 0.08 hours at week 9 (−0.26 hours [95% CI −0.47, −0.05]), corresponding to a 25% reduction. Area under the concentration–time curve from zero to infinity did not change long term (week 0 to year 2) in either the RYGB (1.1 µg h/L [−0.94, 3.2]) or the diet group (0.94 µg h/L [−1.2, 3.0]), despite a considerable difference in weight loss from baseline (RYGB: 30 ± 7%, diet: 3 ± 6%). At baseline, the area under the concentration–time curve from zero to infinity was −5.5 µg h/L [95% CI −8.5, −2.5] (−26%) lower in patients with obesity (RYGB plus diet) than in normal weight individuals scheduled for a cholecystectomy. Further, patients undergoing an RYGB had a 0.05 fmol/µg [95% CI 0.00, 0.10] (29%) higher hepatic P-gp level than the normal weight individuals. Conclusions Changes in digoxin pharmacokinetics following weight loss induced by a pre-operative low-energy diet and an RYGB or a strict diet (a low-energy diet plus a very-low-energy diet) were minor and unlikely to be clinically relevant. The lower systemic exposure of digoxin in patients with obesity suggests that these patients may have increased biliary excretion of digoxin possibly owing to a higher expression of P-gp in the liver.

• Young, Juliet; Seeberg, Kathrine; Aakre, Kristin Moberg; Borgeraas, Heidi; Nordstrand, Njord & Wisløff, Torbjørn [Show all 9 contributors for this article] (2023). The liver-heart axis in patients with severe obesity: The association between liver fibrosis and chronic myocardial injury may be explained by shared risk factors of cardiovascular disease. Clinical Biochemistry. ISSN 0009-9120. 123. doi: 10.1016/j.clinbiochem.2023.110688. Full text in Research Archive Show summary

  Background: Severe obesity is associated with increased risk of non-alcoholic fatty liver disease and cardiovascular disease. We hypothesized that liver fibrosis as quantified by the Enhanced Liver Fibrosis (ELF) test would be predictive of myocardial injury and fibrosis, expressed by high sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI) concentrations. Material and methods: We performed cross-sectional analyses of baseline data from 136 patients (mean age 45 years, 38 % male) with severe obesity participating in the non-randomized clinical trial Prevention of Coronary Heart Disease in Morbidly Obese Patients (ClinicalTrials.gov NCT00626964). Associations between ELF scores, hs-cTnT, and hs-cTnI concentrations were assessed using linear regression analysis. Results: ELF scores were associated with hs-cTnT in the unadjusted model (B 0.381, 95% Confidence Interval [CI] 0.247, 0.514), but the association was attenuated upon adjustment for potential confounders (B -0.031, 95% CI -0.155, 0.093). Similarly, for hs-cTnI, an observed association with ELF scores in the unadjusted model was attenuated upon adjustment for potential confounders ((B 0.432, 95% CI 0.179, 0.685) and (B 0.069, 95% CI -0.230, 0.367), respectively). Age, sex, hypertension, and estimated glomerular filtration rate were amongst the shared predictors of ELF score, hs-cTnT, and hs-cTnI that provided the univariable models with the highest R-squared and lowest Akaike Information Criterion values. Conclusions: Contrary to our hypothesis, ELF score did not predict myocardial injury and fibrosis, but rather demonstrated that an association between liver fibrosis and myocardial injury and fibrosis may be explained by shared risk factors of cardiovascular disease. Keywords: Enhanced Liver Fibrosis test; NT-proBNP; cardiac fibrosis; cardiac troponin; liver fibrosis; myocardial injury; severe obesity.

• Asbjørnsen, Rikke Aune; Hjelmesæth, Jøran Sture; Smedsrød, Mirjam Lien; Wentzel, Jobke; Ollivier, Marianne & Clark, Matthew M. [Show all 8 contributors for this article] (2022). Combining Persuasive System Design Principles and Behavior Change Techniques in Digital Interventions Supporting Long-term Weight Loss Maintenance: Design and Development of eCHANGE. JMIR Human Factors. 9(2). doi: 10.2196/37372. Full text in Research Archive Show summary

  Background: Long-term weight maintenance after weight loss is challenging, and innovative solutions are required. Digital technologies can support behavior change and, therefore, have the potential to be an effective tool for weight loss maintenance. However, to create meaningful and effective digital behavior change interventions that support end user values and needs, a combination of persuasive system design (PSD) principles and behavior change techniques (BCTs) might be needed. Objective: This study aimed to investigate how an evidence-informed digital behavior change intervention can be designed and developed by combining PSD principles and BCTs into design features to support end user values and needs for long-term weight loss maintenance. Methods: This study presents a concept for how PSD principles and BCTs can be translated into design features by combining design thinking and Agile methods to develop and deliver an evidence-informed digital behavior change intervention aimed at supporting weight maintenance. Overall, 45 stakeholders participated in the systematic and iterative development process comprising co-design workshops, prototyping, Agile development, and usability testing. This included prospective end users (n=17, 38%; ie, people with obesity who had lost ≥8% of their weight), health care providers (n=9, 20%), healthy volunteers (n=4, 9%), a service designer (n=1, 2%), and stakeholders from the multidisciplinary research and development team (n=14, 31%; ie, software developers; digital designers; and eHealth, behavior change, and obesity experts). Stakeholder input on how to operationalize the design features and optimize the technology was examined through formative evaluation and qualitative analyses using rapid and in-depth analysis approaches. Results: A total of 17 design features combining PSD principles and BCTs were identified as important to support end user values and needs based on stakeholder input during the design and development of eCHANGE, a digital intervention to support long-term weight loss maintenance. The design features were combined into 4 main intervention components: Week Plan, My Overview, Knowledge and Skills, and Virtual Coach and Smart Feedback System. To support a healthy lifestyle and continued behavior change to maintain weight, PSD principles such as tailoring, personalization, self-monitoring, reminders, rewards, rehearsal, praise, and suggestions were combined and implemented into the design features together with BCTs from the clusters of goals and planning, feedback and monitoring, social support, repetition and substitution, shaping knowledge, natural consequences, associations, antecedents, identity, and self-belief. Conclusions: Combining and implementing PSD principles and BCTs in digital interventions aimed at supporting sustainable behavior change may contribute to the design of engaging and motivating interventions in line with end user values and needs. As such, the design and development of the eCHANGE intervention can provide valuable input for future design and tailoring of evidence-informed digital interventions, even beyond digital interventions in support of health behavior change and long-term weight loss maintenance.

• Hjelmesæth, Jøran Sture; Lund, Randi Størdal; Sagen, Jørn Vegard & Valderhaug, Tone Gretland (2022). Vektreduserende medisiner – for hvem, hvordan, hvor lenge? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.22.0115. Full text in Research Archive Show summary

  Medikamentell behandling av fedme gjennomgår en faglig revolusjon, og det kan være vanskelig å følge med. To relativt nye medikamenter som demper sult og øker metthetsfølelsen, kan nå forskrives av alle leger.

• Hjelmesæth, Jøran Sture & Sjöberg, Agneta (2022). Human body weight, nutrients, and foods: a scoping review. Food & Nutrition Research (FNR). ISSN 1654-6628. 66. doi: 10.29219/fnr.v66.8814. Full text in Research Archive Show summary

  The aim of this article (scoping review) is to elucidate the current knowledge for the potential role of body weight for setting and updating Dietary Reference Values (DRVs) and Food-Based Dietary Guidelines (FBDGs). The following research questions were formulated: What is known about the association between intakes of specific nutrient and/or foods (exposure/intervention) and body weight (outcome) in the general population? What is known about the association between body weight (exposure) and intakes of specific nutrient and/or foods (outcomes)? Is there any evidence suggesting specific effects of foods or nutrients on body weight independent of caloric content? Methods: To identify potentially relevant articles, PubMed was searched from January 1, 2011 to June 9, 2021. The search strategy was drafted by the NNR2022 Committee. The final results were exported into EndNote. Systematic reviews (SRs), scoping reviews (ScRs), reviews, and meta-analyses (MAs) on the topic ‘Body weight’ published between January 1, 2011 and June 9, 2021, including human participants from the general population, in English or Scandinavian language (Norwegian, Swedish, or Danish), were considered eligible. Main findings: First, the overall body of evidence based on findings from SRs and MAs of observational and clinical studies indicates that changes in intakes of specific nutrients (sugar, fiber, and fat) and/or foods (sugar sweetened beverages, fiber rich food, and vegetables) are associated with modest or small short-term changes (0.3–1.3 kg) in body weight in the general population (with or without obesity/overweight), while long-term studies are generally lacking. Second, no study in our search assessed any association between body weight (exposure) and intakes of specific nutrients or foods (outcomes). Third, limited evidence suggests, but does not prove, that some foods or nutrients may have specific effects on body weight or body weight measures independent of caloric content (e.g. nuts and dairy). These findings may inform the setting and updating of DRVs and FBDGs in NNR2022.

• Kvitne, Kine Eide; Hole, Kristine; Krogstad, Veronica; Wollmann, Birgit Malene Tovik; Wegler, Christine & Johnson, Line Kristin [Show all 19 contributors for this article] (2022). Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range. European Journal of Clinical Pharmacology. ISSN 0031-6970. 78(8), p. 1289–1299. doi: 10.1007/s00228-022-03336-9. Full text in Research Archive Show summary

  Purpose Variability in cytochrome P450 3A4 (CYP3A4) metabolism is mainly caused by non-genetic factors, hence providing a need for accurate phenotype biomarkers. Although 4β-hydroxycholesterol (4βOHC) is a promising endogenous CYP3A4 biomarker, additional investigations are required to evaluate its ability to predict CYP3A4 activity. This study investigated the correlations between 4βOHC concentrations and hepatic and intestinal CYP3A4 protein expression and ex vivo microsomal activity in paired liver and jejunum samples, as well as in vivo CYP3A4 phenotyping (midazolam) in patients with a wide body weight range. Methods The patients (n = 96; 78 with obesity and 18 normal or overweight individuals) were included from the COCKTAIL-study (NCT02386917). Plasma samples for analysis of 4βOHC and midazolam concentrations, and liver (n = 56) and jejunal (n = 38) biopsies were obtained. The biopsies for determination of CYP3A4 protein concentration and microsomal activity were obtained during gastric bypass or cholecystectomy. In vivo CYP3A4 phenotyping was performed using semi-simultaneous oral (1.5 mg) and intravenous (1.0 mg) midazolam. Results 4βOHC concentrations were positively correlated with hepatic microsomal CYP3A4 activity (ρ = 0.53, p < 0.001), and hepatic CYP3A4 concentrations (ρ = 0.30, p = 0.027), but not with intestinal CYP3A4 concentrations (ρ = 0.18, p = 0.28) or intestinal microsomal CYP3A4 activity (ρ = 0.15, p = 0.53). 4βOHC concentrations correlated weakly with midazolam absolute bioavailability (ρ =  − 0.23, p = 0.027) and apparent oral clearance (ρ = 0.28, p = 0.008), but not with systemic clearance (ρ =  − 0.03, p = 0.81). Conclusion These findings suggest that 4βOHC concentrations reflect hepatic, but not intestinal, CYP3A4 activity. Further studies should investigate the potential value of 4βOHC as an endogenous biomarker for individual dose requirements of intravenously administered CYP3A4 substrate drugs.

• Haugstøyl, Martha Eimstad; Cornillet, Martin; Strand, Kristina; Stiglund, Natalie; Sun, Dan & Dyer, Laurence [Show all 15 contributors for this article] (2022). Distinct T cell subsets in adipose tissue are associated with obesity. European Journal of Immunology. ISSN 0014-2980. doi: 10.1002/eji.202249990. Full text in Research Archive Show summary

  Adipose tissue inflammation is a driving factor for the development of obesity-associated metabolic disturbances, and a role of adipose tissue T cells in initiating the pro-inflammatory signaling is emerging. However, data on human adipose tissue T cells in obesity are limited, reflected by the lack of phenotypic markers to define tissue-resident T cell subsets. In this study, we performed a deep characterization of T cells in blood and adipose tissue depots using multicolor flow cytometry and RNA sequencing. We identified distinct subsets of T cells associated with obesity expressing the activation markers, CD26 and CCR5, and obesity-specific genes that are potentially engaged in activating pro-inflammatory pathway, including ceramide signaling, autophagy, and IL-6 signaling. These findings increase our knowledge on the heterogeneity of T cells in adipose tissue and on subsets that may play a role in obesity-related pathogenesis.

• Kvitne, Kine Eide; Krogstad, Veronica; Wegler, Christine; Johnson, Line Kristin; Kringen, Marianne K. & Hovd, Markus Herberg [Show all 19 contributors for this article] (2022). Short- and long-term effects of body weight, calorie restriction and gastric bypass on CYP1A2, CYP2C19 and CYP2C9 activity. British Journal of Clinical Pharmacology. ISSN 0306-5251. 88(9), p. 4121–4133. doi: 10.1111/bcp.15349. Full text in Research Archive Show summary

  Roux-en-Y gastric bypass (RYGB) may influence drug disposition due to surgery-induced gastrointestinal alterations and/or subsequent weight loss. The objective was to compare short- and long-term effects of RYGB and diet on the metabolic ratios of paraxanthine/caffeine (cytochrome P450 [CYP] 1A2 activity), 5-hydroxyomeprazole/omeprazole (CYP2C19 activity) and losartan/losartan carboxylic acid (CYP2C9 activity), and cross-sectionally compare these CYP-activities with normal-to-overweight controls. Methods This trial included patients with severe obesity preparing for RYGB (n = 40) or diet-induced (n = 41) weight loss, and controls (n = 18). Both weight loss groups underwent a 3-week low-energy diet (<1200 kcal/day, weeks 0-3) followed by a 6-week very-low-energy diet or RYGB (both <800 kcal/day, weeks 3-9). Follow-up time was 2 years, with four pharmacokinetic investigations. Results Mean ± SD weight loss from baseline was similar in the RYGB-group (13 ± 2.4%) and the diet group (10.5 ± 3.9%) at week 9, but differed at year 2 (RYGB −30 ± 6.9%, diet −3.1 ± 6.3%). From weeks 0 to 3, mean (95% confidence interval [CI]) CYP2C19 activity similarly increased in both groups (RYGB 43% [16, 55], diet 48% [22, 60]). Mean CYP2C19 activity increased by 30% (2.6, 43) after RYGB (weeks 3-9), but not in the diet-group (between-group difference −0.30 [−0.63, 0.03]). CYP2C19 activity remained elevated in the RYGB group at year 2. Baseline CYP2C19 activity was 2.7-fold higher in controls compared with patients with obesity, whereas no difference was observed in CYP1A2 and CYP2C9 activities. Conclusion Our findings suggest that CYP2C19 activity is lower in patients with obesity and increases following weight loss. This may be clinically relevant for drug dosing. No clinically significant effect on CYP1A2 and CYP2C9 activities was observed.

• Wegler, Christine; Wisniewski, Jacek R.; Robertsen, Ida; Christensen, Hege; Hertel, Jens Kristoffer & Hjelmesæth, Jøran Sture [Show all 10 contributors for this article] (2022). Drug disposition protein quantification in matched human jejunum and liver from donors with obesity. Clinical Pharmacology and Therapeutics. ISSN 0009-9236. 111(5), p. 1142–1154. doi: 10.1002/cpt.2558. Full text in Research Archive Show summary

  Mathematical models, such as physiologically based pharmacokinetic (PBPK) models, are used to predict e.g., drug disposition and toxicity. However, populations differ in the abundance of proteins involved in these processes. To improve the building and refinement of such models, they must take into account these inter-individual variabilities. In this study, we used global proteomics to characterize the protein composition of jejunum and liver from 37 donors with obesity enrolled in the COCKTAIL study. Liver protein levels from the 37 donors were further compared with those from donors without obesity. We quantified thousands of proteins and could present the expression of several drug-metabolizing enzymes, for the first time, in jejunum, many of which belong to the cytochrome P450 (e.g., CYP2U1) and the amine oxidase [flavin-containing] (e.g., MAOA) families. Although we show that many metabolizing enzymes had greater expression in liver, others had higher expression in jejunum (such as, MAOA and CES2), indicating the role of the small intestine in extrahepatic drug metabolism. We further show that proteins involved in drug disposition are not correlated in the two donor-matched tissues. These proteins also do not correlate with physiological factors such as BMI, age, and inflammation status in either tissue. Furthermore, the majority of these proteins are not differently expressed in donors with or without obesity. Nonetheless, inter-individual differences were considerable, with implications for personalized prediction models and systems pharmacology.

• Rolin, Johannes; Ødegård, Rønnaug; Amundsen, Viktoria Vedeler; Køpp, Unni Mette; Kokkvoll, Ane Sofie & Juliusson, Pétur Benedikt [Show all 7 contributors for this article] (2022). Medikamentell tilleggsbehandling for vektreduksjon hos ungdom med alvorlig fedme. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 142(14), p. 1–3. doi: 10.4045/tidsskr.22.0540. Full text in Research Archive
• Pfabigan, Daniela Melitta; Hertel, Jens Kristoffer; Svanevik, Marius; Lindberg, Morten; Sailer, Uta & Hjelmesæth, Jøran Sture (2022). Single-centre, non-randomised clinical trial to investigate the effects of bariatric surgery on social experiences and biomarkers of well-being one year after surgery in individuals with severe obesity: a protocol for the Bariatric Surgery and Social Experiences (BaSES) study. medRxiv. doi: 10.1101/2022.12.21.22283770. Full text in Research Archive Show summary

  Introduction Obesity is linked to increased loneliness and less enjoyment of social interactions. While bariatric surgery is the most effective treatment targeting morbid obesity, there is limited understanding as to whether patients experience social interactions differently after surgery. The Bariatric Surgery and Social Experiences Study (BaSES) is designed to assess potential changes in how much patients enjoy and engage in daily social interactions 1 year after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Methods and analysis Single-centre, non-randomised clinical trial carried out at the Morbid Obesity Centre at Vestfold Hospital Trust, Norway. Eligible patients will undergo either RYGB, SG or single anastomosis sleeve ileal bypass (SASI). The primary outcome measure is change in the social experience score (assessed with a questionnaire) from a pre-surgery to a follow-up assessment 1 year after RYGB and SG. The respective changes after SASI will be assessed and considered exploratory. Ethics and dissemination The most recent protocol version of this study was reviewed and approved by the Regional Committee for Medical Research Ethics South East Norway (REK sør-øst A) on the 29th of August 2022 (ref: 238406). The results will be disseminated to academic and health professional audiences and the public via publications in international peer-reviewed journals and conferences. Trial registration number NCT05207917 (ClinicalTrials.gov)

• Berk, Kirsten A.; Borgeraas, Heidi; Narverud, Ingunn; Mulder, Monique T.; Øyri, Linn Kristin Lie & Verhoeven, Adrie J M [Show all 14 contributors for this article] (2022). Differential effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) and fatty acids. Lipids in Health and Disease. 21(145), p. 1–14. doi: 10.1186/s12944-022-01756-1. Full text in Research Archive Show summary

  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. Methods 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). Results 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). Conclusion 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).

• Fatima, Farhat; Hjelmesæth, Jøran Sture; Hertel, Jens Kristoffer; Svanevik, Marius; Sandbu, Rune & Småstuen, Milada Cvancarova [Show all 7 contributors for this article] (2022). Validation of Ad-DiaRem and ABCD Diabetes Remission Prediction Scores at 1-Year After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in the Randomized Controlled Oseberg Trial. Obesity Surgery. ISSN 0960-8923. 32(3), p. 801–809. doi: 10.1007/s11695-021-05856-2. Full text in Research Archive Show summary

  Background Prediction of type 2 diabetes (T2DM) remission is an important part of risk-benefit assessment before bariatric surgery. Study Design 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. Results 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. Conclusion 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.

• Kvitne, Kine Eide; Åsberg, Anders; Johnson, Line Kristin; Wegler, Christine; Hertel, Jens Kristoffer & Artursson, Per [Show all 14 contributors for this article] (2022). Impact of type 2 diabetes on in vivo activities and protein expressions of cytochrome P450 in patients with obesity. Clinical and Translational Science (CTS). ISSN 1752-8054. 15(11), p. 2685–2696. doi: 10.1111/cts.13394. Full text in Research Archive Show summary

  Previous studies have not accounted for the close link between type 2 diabetes mellitus (T2DM) and obesity when investigating the impact of T2DM on cytochrome P450 (CYP) activities. The aim was to investigate the effect of T2DM on in vivo activities and protein expressions of CYP2C19, CYP3A, CYP1A2, and CYP2C9 in patients with obesity. A total of 99 patients from the COCKTAIL study (NCT02386917) were included in this cross-sectional analysis; 29 with T2DM and obesity (T2DM-obesity), 53 with obesity without T2DM (obesity), and 17 controls without T2DM and obesity (controls). CYP activities were assessed after the administration of a cocktail of probe drugs including omeprazole (CYP2C19), midazolam (CYP3A), caffeine (CYP1A2), and losartan (CYP2C9). Jejunal and liver biopsies were also obtained to determine protein concentrations of the respective CYPs. CYP2C19 activity and jejunal CYP2C19 concentration were 63% (−0.39 [95% CI: −0.82, −0.09]) and 40% (−0.09 fmol/μg protein [95% CI: −0.18, −0.003]) lower in T2DM-obesity compared with the obesity group, respectively. By contrast, there were no differences in the in vivo activities and protein concentrations of CYP3A, CYP1A2, and CYP2C9. Multivariable regression analyses also indicated that T2DM was associated with interindividual variability in CYP2C19 activity, but not CYP3A, CYP1A2, and CYP2C9 activities. The findings indicate that T2DM has a significant downregulating impact on CYP2C19 activity, but not on CYP3A, CYP1A2, and CYP2C9 activities and protein concentrations in patients with obesity. Hence, the effect of T2DM seems to be isoform-specific.

• Berge, Jarle; Hjelmesæth, Jøran Sture; Kolotkin, Ronette Loganzo; Støren, Øyvind; Bratland-Sanda, Solfrid & Hertel, Jens Kristoffer [Show all 10 contributors for this article] (2022). Effect of aerobic exercise intensity on health-related quality of life in severe obesity: a randomized controlled trial. Health and Quality of Life Outcomes. 20. doi: 10.1186/s12955-022-01940-y. Full text in Research Archive Show summary

  Background Aerobic exercise is an important part of obesity treatment and may improve health-related quality of life (HRQOL). The objective of this study was to compare the effect of two different exercise programs on health-related quality of life in patients with severe obesity. Methods This was a single-center, open-label, randomized, parallel-group study comparing the effects of a 24-week moderate-intensity continuous training (MICT) program and a combined high-intensity interval training program with MICT (HIIT/MICT). The primary objective (specified secondary outcome) was to assess HRQOL by using the general health dimension of the Short Form Health Survey (SF-36). The secondary objectives were to assess other dimensional SF-36 scores, the impact of weight on the physical and psychosocial aspects of quality of life (IWQOL-Lite), and the burden of obesity-specific weight symptoms (WRSM). Results 73 patients were enrolled and reported patient reported outcome measures, with 71 patients (55% females) allocated to either MICT (n = 34) or HIIT/MICT (n = 37). In the intention-to-treat analysis, general health scores increased between baseline and 24-week follow-up in both the HIIT/MICT group and the MICT group, with a mean change of 13 (95% CI 6–21) points and 11 (95% CI 5–17) points, respectively, with no difference between the groups. The effect sizes of these changes were moderate. The vitality and social functioning scores of SF-36, and the physical function and self-esteem scores of IWQOL-Lite increased moderately in both groups, with no difference between groups. The tiredness, back pain, and physical stamina scores based on WRSM showed moderate to strong changes in both the groups. Conclusions Patients who had completed a combined HIIT/MICT program did not experience larger improvements in general health compared with those completing a clean 24-week MICT program. Exercise may confer general health benefits independent of intensity.

• Seeberg, Kathrine; Hofsø, Dag; Borgeraas, Heidi; Grimnes, John Olav; Fatima, Farhat & Seeberg, Lars Thomas [Show all 10 contributors for this article] (2022). Association between hepatic steatosis and fibrosis with measures of insulin sensitivity in patients with severe obesity and type 2 diabetes - a cross-sectional study. BMC Gastroenterology. 22(1). doi: 10.1186/s12876-022-02550-0. Full text in Research Archive Show summary

  Obesity, non-alcoholic fatty liver disease (NAFLD) and insulin resistance are three pathological conditions highly correlated, but this relationship is not fully elucidated. Hence, we aimed to assess the association of hepatic steatosis and fibrosis with different measures of insulin sensitivity in patients with severe obesity and type 2 diabetes mellitus (T2DM). Methods A cross-sectional study (Oseberg trial) including patients with T2DM referred for bariatric surgery at Vestfold Hospital Trust, Norway. Magnetic resonance imaging (MRI) and the enhanced liver fibrosis (ELF) test was used for estimation of liver fat fraction (LFF) and degree of fibrosis, respectively. Oral and intravenous glucose tolerance tests were applied for estimation of insulin sensitivity (HOMA2S, Matsuda ISI and MinMod SI). Results A total of 100 patients (mean [SD] age 47.5 [9.7] years, 65% women, BMI 42.0 [5.3] kg/m2 and 98% with metabolic syndrome) were included in the analyses. The mean (SD) LFF in the total population was 19.1 (11.5), and the mean (SD) ELF score was 8.46 (0.84), a value representing moderate fibrosis. LFF was inversely associated with HOMA2S and Matsuda ISI, and both measures were significantly higher in the no or low-grade steatosis group compared with the medium-to-high grade steatosis group (mean difference [95% CI] 5.9 [2.2-9.6]%, Cohen’s d = 0.75), and (0.7 [0.3-1.1], Cohen’s d = 0.80, respectively). There was no association between LFF, as a categorical or continuous variable, and MinMod SI. The proportions of patients with none to mild fibrosis, moderate fibrosis and severe fibrosis were 14, 78 and 6%, respectively, and there were no significant associations between level of fibrosis and measures of insulin sensitivity. Conclusions Patients with morbid obesity and T2DM demonstrated high levels of liver fat fraction, and we showed that hepatic steatosis, but not the degree of liver fibrosis, was associated with different measures of insulin sensitivity in patients with severe obesity and T2DM. Further, our results might indicate that the LFF is primarily associated with hepatic, and not peripheral insulin sensitivity. To improve the diagnosis of NAFLD and the prediction of its progression, more studies are needed to reveal the pathological mechanistic pathways involved in NAFLD and insulin sensitivity.

• Barstad, Lisa Ah Fung Ha; Johnson, Line Kristin; Borgeraas, Heidi; Hofsø, Dag; Svanevik, Marius & Småstuen, Milada Cvancarova [Show all 8 contributors for this article] (2022). Changes in dietary intake, food tolerance, hedonic hunger, binge eating problems, and gastrointestinal symptoms after sleeve gastrectomy compared with after gastric bypass; 1-year results from the Oseberg study—a randomized controlled trial. American Journal of Clinical Nutrition. ISSN 0002-9165. 117(3), p. 586–598. doi: 10.1016/j.ajcnut.2022.11.016. Full text in Research Archive Show summary

  Background The randomized Oseberg study compared the effects of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the 1-year remission of type 2 diabetes and beta-cell function (primary outcomes). However, little is known about the comparable effects of SG and RYGB on changes in dietary intakes, eating behavior, and gastrointestinal discomfort. Objective To compare 1-year changes in intakes of macro- and micronutrients, food groups, food tolerance, hedonic hunger, binge eating and gastrointestinal symptoms after SG and RYGB. Methods Among others, prespecified secondary outcomes were dietary intake, food tolerance, hedonic hunger, binge eating and gastrointestinal symptoms assessed with the Food frequency questionnaire, Food tolerance questionnaire, Power of food scale, Binge eating scale, and Gastrointestinal symptom rating scale, respectively. Results A total of 109 patients (66 % females) with mean (SD) age 47.7 (9.6) years and BMI of 42.3 (5.3) kg/m2, were allocated to SG (n=55) or RYGB (n=54). The SG group had, compared with the RYGB group, greater 1-year reductions in intakes of: Protein, mean (95 % CI) between group difference, -13 (-24.9, -1.2) g; fiber, -4.9 (-8.2, -1.6) g; magnesium, -77 (-147, -6) mg; potassium, -640 (-1237, -44) mg; and fruits and berries, -65 (-109, -20) g. Further, the intake of yoghurt and fermented milk products was more than doubled after RYGB but unchanged after SG. In addition, hedonic hunger and binge eating problems declined similarly after both surgeries, while most gastrointestinal symptoms and food tolerance remained stable at 1 year. Conclusions The 1-year changes in dietary intakes of fiber and proteins after both surgical procedures, but particularly after SG, were unfavorable with regard to current dietary guidelines. For clinical practice, our findings suggest that health care providers and patients should focus on sufficient intakes of protein, fiber, and vitamin-and mineral supplementation after both SG and RYGB.

• Berge, Jarle; Hjelmesæth, Jøran; Hertel, Jens Kristoffer; Gjevestad, Espen Svendsen; Småstuen, Milada Cvancarova & Johnson, Line Kristin [Show all 10 contributors for this article] (2021). Effect of Aerobic Exercise Intensity on Energy Expenditure and Weight Loss in Severe Obesity-A Randomized Controlled Trial. Obesity. ISSN 1930-7381. 29(2), p. 359–369. doi: 10.1002/oby.23078. Full text in Research Archive Show summary

  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.

• Fatima, Farhat; Hjelmesæth, Jøran Sture; Birkeland, Kåre Inge; Gulseth, Hanne Løvdal; Hertel, Jens Kristoffer & Svanevik, Marius [Show all 11 contributors for this article] (2021). Gastrointestinal hormones and β-cell function after gastric bypass and sleeve gastrectomy: a randomized controlled trial (Oseberg). Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. 107(2), p. e756–e766. doi: 10.1210/clinem/dgab643. Full text in Research Archive Show summary

  Context Whether Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) differentially affect postprandial gastrointestinal hormones and β-cell function in type 2 diabetes remains unclear. Objective To compare gastrointestinal hormones and β-cell function assessed by an oral glucose tolerance test (OGTT) 5 weeks and 1 year after surgery hypothesizing higher GLP-1 levels and greater β-cell response to glucose after RYGB than after SG. Design, Setting, Patients, and Interventions Randomized, triple blind, single-center trial at a tertiary care center in Norway. Primary outcomes; diabetes remission and IVGTT derived β-cell function. Participants with obesity and type 2 diabetes allocated (1:1) to RYGB or SG. Main outcome measures Gastrointestinal hormone profiles and insulin secretion [β-cell glucose sensitivity (β-GS)] derived from 180 minutes OGTTs. Results 106 patients (67% women), mean (SD) age 48 (10) years. Diabetes remission rates at 1-year were higher after RYGB than after SG, 77% versus 48%, p = 0.002. Incremental area under the curve (iAUC0-180) glucagon-like peptide-1 (GLP-1) and β-GS increased more after RYGB than after SG, 1-year between-group difference 1173 pmol/l*min (95% CI 569 to 1776), p = 0.0010, and 0.45 pmol/kg/min/mmol (95% CI 0.15 to 0.75), p = 0.0032, respectively. Post-surgery, fasting and postprandial ghrelin levels were higher and decremental AUC0-180 ghrelin, iAUC0-180 glucose-dependent insulinotropic polypeptide, and iAUC0-60 glucagon were greater after RYGB than after SG. Diabetes remission at 1 year was associated with higher β-GS and higher GLP-1 secretion. Conclusions RYGB was associated with greater improvement in β-cell function and higher postprandial GLP-1 levels than SG.

• Seeberg, Kathrine; Borgeraas, Heidi; Hofsø, Dag; Småstuen, Milada Cvancarova; Kvan, Nils Petter & Grimnes, John Olav [Show all 12 contributors for this article] (2021). Gastric Bypass Versus Sleeve Gastrectomy in Type 2 Diabetes: Effects on Hepatic Steatosis and Fibrosis A Randomized Controlled Trial. Annals of Internal Medicine. ISSN 0003-4819. 175(1), p. 74–83. doi: 10.7326/M21-1962. Full text in Research Archive Show summary

  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 Tønsberg]). (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.

• Salte, Odd Bjørn; Svanevik, Marius; Risstad, Hilde; Hofsø, Dag; Høgestøl, Ingvild Kristine & Johnson, Line Kristin [Show all 11 contributors for this article] (2021). Standard versus distal Roux-en-Y gastric bypass in patients with BMI 50–60 kg/m2: 5-year outcomes of a double-blind, randomized clinical trial. BJS Open. 5(6), p. 1–9. doi: 10.1093/bjsopen/zrab105. Full text in Research Archive Show summary

  Background The optimal surgical weight loss procedure for patients with a BMI of 50 kg/m2 or more is uncertain. This study compared distal Roux-en-Y gastric bypass (RYGB) with standard RYGB. Methods In this double-blind RCT, patients aged 18–60 years with a BMI of 50–60 kg/m2 were allocated randomly to receive standard (150 cm alimentary, 50 cm biliopancreatic limb) or distal (150 cm common channel, 50 cm biliopancreatic limb) RYGB. The primary outcome (change in BMI at 2 years) has been reported previously. Secondary outcomes 5 years after surgery, such as weight loss, health-related quality of life, and nutritional outcomes are reported. Results Between May 2011 and April 2013, 123 patients were randomized, 113 received an intervention, and 92 attended 5-year follow-up. Mean age was 40 (95 per cent c.i. 38 to 41) years and 73 patients (65 per cent) were women; 57 underwent standard RYGB and 56 distal RYGB. BMI was reduced by 15.1 (95 per cent c.i. 13.9 to 16.2) kg/m2 after standard and 15.7 (14.5 to 16.9) kg/m2 after distal RYGB; the between-group difference was −0.64 (−2.3 to 1.0) kg/m2 (P = 0.447). Total cholesterol, low-density lipoprotein cholesterol, and haemoglobin A1c levels declined more after distal than after standard RYGB. High-density lipoprotein cholesterol levels increased more after standard RYGB. Vitamin A and vitamin D levels were lower after distal RYGB. Changes in bone mineral density, resting metabolic rate, and total energy intake were comparable. Conclusion Distal RYGB did not enable greater weight loss than standard RYGB. Differences in other outcomes favouring distal RYGB may not justify routine use of this procedure in patients with a BMI of 50–60 kg/m2.

• Tønnesen, Christer Julseth; Hjelmesæth, Jøran; Hofsø, Dag; Tonstad, Serena; Hertel, Jens Kristoffer & Heggen, Eli [Show all 14 contributors for this article] (2021). A novel intragastric balloon for treatment of obesity and type 2 diabetes. A two-center pilot trial. Scandinavian Journal of Gastroenterology. ISSN 0036-5521. 57(2), p. 232–238. doi: 10.1080/00365521.2021.1994641. Full text in Research Archive Show summary

  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. <p> <p>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. <p> <p>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. <p> <p>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.

• Kvitne, Kine Eide; Robertsen, Ida; Skovlund, Eva; Christensen, Hege Staaland; Krogstad, Veronica & Wegler, Christine [Show all 18 contributors for this article] (2021). Short- and long-term effects of body weight loss following calorie restriction and gastric bypass on CYP3A-activity – a non-randomized three-armed controlled trial. Clinical and Translational Science (CTS). ISSN 1752-8054. doi: 10.1111/cts.13142. Full text in Research Archive Show summary

  It remains uncertain whether pharmacokinetic changes following Roux-en-Y gastric bypass (RYGB) can be attributed to surgery-induced gastrointestinal alterations per se and/or the subsequent weight loss. The aim was to compare short- and long-term effects of RYGB and calorie restriction on CYP3A-activity, and cross-sectionally compare CYP3A-activity with normal weight to overweight controls using midazolam as probe drug. This three-armed controlled trial included patients with severe obesity preparing for RYGB (n = 41) or diet-induced (n = 41) weight-loss, and controls (n = 18). Both weight-loss groups underwent a 3-week low-energy-diet (<1200 kcal/day) followed by a 6-week very-low-energy-diet or RYGB (both <800 kcal/day). Patients were followed for 2 years, with four pharmacokinetic investigations using semisimultaneous oral and intravenous dosing to determine changes in midazolam absolute bioavailability and clearance, within and between groups. The RYGB and diet groups showed similar weight-loss at week 9 (13 ± 2.4% vs. 11 ± 3.6%), but differed substantially after 2 years (−30 ± 7.0% vs. −3.1 ± 6.3%). At baseline, mean absolute bioavailability and clearance of midazolam were similar in the RYGB and diet groups, but higher compared with controls. On average, absolute bioavailability was unaltered at week 9, but decreased by 40 ± 7.5% in the RYGB group and 32 ± 6.1% in the diet group at year 2 compared with baseline, with no between-group difference. No difference in clearance was observed over time, nor between groups. In conclusion, neither RYGB per se nor weight loss impacted absolute bioavailability or clearance of midazolam short term. Long term, absolute bioavailability was similarly decreased in both groups despite different weight loss, suggesting that the recovered CYP3A-activity is not only dependent on weight-loss through RYGB.

• Lorentzen, Jolanta Halabowska; Medhus, Asle Wilhelm; Hofsø, Dag; Svanevik, Marius; Seip, Birgitte Karen Berggreen & Hjelmesæth, Jøran (2021). Sleeve gastrectomy confers higher risk of gastroesophageal reflux disease than gastric bypass. A Randomized Controlled Trial From the Oseberg Reflux Working Group. Gastroenterology. ISSN 0016-5085. 161(6), p. 2044–2046. doi: 10.1053/j.gastro.2021.08.021. Full text in Research Archive
• Borgeraas, Heidi; Hofsø, Dag; Hertel, Jens Kristoffer & Hjelmesæth, Jøran (2020). Comparison of the effect of Roux-en-Y gastric bypass and sleeve gastrectomy on remission of type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Obesity Reviews. ISSN 1467-7881. 21(6). doi: 10.1111/obr.13011. Full text in Research Archive Show summary

  Bariatric surgery is an effective treatment option for patients with type 2 diabetes mellitus (T2DM) and obesity. This study aims to compare the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on remission of T2DM. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies published between database inception and 21 November 2019. A meta-analysis, using a random effects model, was performed to calculate relative risk (RR) of T2DM remission between the groups in randomized controlled trials (RCTs). Of 2650 records identified, 12 records from 10 different RCTs were finally included. The studies comprised 705 patients with follow-up from 1 to 5 years. The remission rate of T2DM at 1 year was higher among those undergoing RYGB (156/276, 57%) compared with those undergoing SG (128/275, 47%), RR (95% CI) 1.20 (1.00-1.45), P = .047, I2 = 24.9%, moderate-quality evidence. Among studies with 2- to 5-year follow-up, there was no difference in remission rates between the RYGB (132/263, 50%) and SG (121/266, 46%) groups, RR 1.06 (0.94-1.20), P = .34, I2 = 0.0%, low-quality evidence. RYGB resulted in a higher rate of T2DM remission compared with SG after 1 year. The T2DM remission rates did not differ in studies with 2- to 5-year follow-up

• Hofsø, Dag; Hillestad, Thor Olav Widerøe; Halvorsen, Erling; Fatima, Farhat; Johnson, Line Kristin & Lindberg, Morten [Show all 9 contributors for this article] (2020). Bone Mineral Density and Turnover After Sleeve Gastrectomy and Gastric Bypass: A Randomized Controlled Trial (Oseberg). Journal of Clinical Endocrinology and Metabolism (JCEM). ISSN 0021-972X. doi: 10.1210/clinem/dgaa808. Full text in Research Archive Show summary

  Context Bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB), is associated with increased risk of osteoporotic fractures. It is unknown whether RYGB or sleeve gastrectomy (SG) have different effects on bone health. Objective To compare changes in bone mineral density and markers of bone turnover one year after SG and RYGB. Design, Setting, Patients, and Interventions Randomized, triple-blind, single-center trial at a tertiary care center in Norway. Primary outcome was diabetes remission. Patients with severe obesity and type 2 diabetes were randomized and allocated (1:1) to SG or RYGB. Main Outcome Measures Changes in areal bone mineral density (aBMD) and bone turnover markers. Results Femoral neck, total hip, and lumbar spine aBMD, but not total body aBMD, decreased significantly more after RYGB (n=44) than after SG (n=48) [mean (95% CI) between group differences -2.8 % (-0.8 to -4.7), -3.0 % (-0.9 to -5.0), -4.2 % (-2.1 to -6.4), and -0.5 % (0.6 to -1.6), respectively]. The increase in procollagen type 1 N-terminal propeptide (P1NP) and C-telopeptide of type I collagen (CTX-1) were approximately 100% higher after RYGB than after SG, (both time x group, P<0.001). The changes in femoral neck, total hip and lumbar spine aBMDs and the changes in P1NP and CTX-1 were independently associated with the surgical procedure (all P<0.05) and not weight change. Conclusions RYGB was associated with greater reduction in aBMD and greater increase in bone turnover markers compared with SG. This finding could suggest greater skeletal fragility after RYGB.

• Skodvin, Vilde Aabel; Lekhal, Samira; Kommedal, Kristin Garpestad; Benestad, Beate; Skjåkødegård, Hanna Flækøy & Danielsen, Yngvild Sørebø [Show all 11 contributors for this article] (2020). Livsstilsbehandling av barn og ungdom med alvorlig fedme – resultater etter ett år. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.19.0682. Full text in Research Archive Show summary

  BAKGRUNN Internasjonalt er livsstilsbehandling av barn og unge med alvorlig fedme vist å ha moderate korttidseffekter på vektreduksjon. Vi evaluerte behandlingsresultater ved to norske spesialistpoliklinikker. MATERIALE OG METODE Vi gjorde en retrospektiv analyse av innsamlede data for perioden 2012–16. Barn med alvorlig fedme som møtte til ettårskontroll, ble inkludert. I analysene inkluderte vi kroppsvektmålene prosentdel av definisjonen til overvekt (%IOTF-25), BMI-standardavviksskår, midjemålstandardavviksskår og kroppsfettprosent ved behandlingsstart og ved ettårskontroll. RESULTATER Av 568 barn som startet behandling, møtte 416 (73 %) i alderen 3–18 år til ettårskontroll og ble inkludert. Flertallet av pasientene, totalt 271 (65 %), oppnådde reduksjon i %IOTF-25, mens 228 pasienter (55 %) reduserte sin BMI-standardavviksskår. Det var en statistisk signifikant gjennomsnittlig reduksjon for alle fire registrerte kroppsvektmål. Totalt 54 av 325 barn (17 %) endret kategori fra alvorlig fedme til fedme, 8 (2 %) gikk fra alvorlig fedme til overvekt, og 8 av 91 barn (9 %) endret kategori fra fedme til overvekt eller normal vekt. Andelen deltagere med mer enn 5 % reduksjon i %IOTF-25 var 43 % (177/416), og en reduksjon i BMI-standardavviksskår på mer enn 0,25 ble observert hos 23 % (95/416). Samtlige utfallsmål viste at jenter responderte dårligere på behandling enn gutter og at det ikke var noen klinisk viktig forskjell i resultater mellom behandlingssentrene. FORTOLKNING Etter ett års behandling av barn og unge med alvorlig fedme i spesialisthelsetjenesten fant vi moderate gjennomsnittlige reduksjoner i vekt, midjemål og kroppsfettprosent, men med stor interindividuell variasjon.

• Krogstad, Veronica; Peric, Alexandra; Robertsen, Ida; Kringen, Marianne K.; Vistnes, Maria & Hjelmesæth, Jøran [Show all 15 contributors for this article] (2020). Correlation of body weight and composition with hepatic activities of cytochrome P450 enzymes. Journal of Pharmaceutical Sciences. ISSN 0022-3549. 110(1), p. 432–437. doi: 10.1016/j.xphs.2020.10.027. Full text in Research Archive Show summary

  Obesity is associated with comorbidities of which pharmacological treatment is needed. Physiological changes associated with obesity may influence the pharmacokinetics of drugs, but the effect of body weight on drug metabolism capacity remains uncertain. The aim of this study was to investigate ex vivo activities of hepatic drug metabolizing CYP enzymes in patients covering a wide range of body weight. Liver biopsies from 36 individuals with a body mass index (BMI) ranging from 18 to 63 kg/m2 were obtained. Individual hepatic microsomes were prepared and activities of CYP3A, CYP2B6, CYP2C8, CYP2D6, CYP2C9, CYP2C19 and CYP1A2 were determined. The unbound intrinsic clearance (CLint,u) values for CYP3A correlated negatively with body weight (r = −0.43, p < 0.01), waist circumference (r = −0.47, p < 0.01), hip circumference (r = −0.51, p < 0.01), fat percent (r = −0.41, p < 0.05), fat mass (r = −0.48, p < 0.01) and BMI (r = −0.46, p < 0.01). Linear regression analysis showed that CLint,u values for CYP3A decreased with 5% with each 10% increase in body weight (r2 = 0.12, β = −0.558, p < 0.05). There were no correlations between body weight measures and CLint,u values for the other CYP enzymes investigated. These results indicate reduced hepatic metabolizing capacity of CYP3A substrates in patients with increasing body weight.

• Hjelmesæth, Jøran & Skaare, Dagfinn (2020). Covid-19 med nedsatt lukte-og smakssans som eneste symptom. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 140(7). doi: 10.4045/TIDSSKR.20.0287. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Wentzel, Jobke; Smedsrød, Mirjam Lien; Hjelmesæth, Jøran; Clark, Matthew M. & Nes, Lise Solberg [Show all 7 contributors for this article] (2020). Identifying Persuasive Design Principles and Behavior Change Techniques Supporting End User Values and Needs in eHealth Interventions for Long-Term Weight Loss Maintenance: Qualitative Study. Journal of Medical Internet Research (JMIR). ISSN 1439-4456. 22(11). doi: 10.2196/22598. Full text in Research Archive Show summary

  Background An increasing number of eHealth interventions aim to support healthy behaviors that facilitate weight loss. However, there is limited evidence of the effectiveness of the interventions and little focus on weight loss maintenance. Knowledge about end user values and needs is essential to create meaningful and effective eHealth interventions, and to identify persuasive system design (PSD) principles and behavior change techniques (BCTs) that may contribute to the behavior change required for successful long-term weight loss maintenance. Objective This study aimed to provide insight into the design of eHealth interventions supporting behavior change for long-term weight maintenance. The study sought to identify the values and needs of people with obesity aiming to maintain weight after weight loss, and to identify PSD principles, BCTs, and design requirements that potentially enable an eHealth intervention to meet end user values and needs. Methods This study presents the concept of integrating PSD principles and BCTs into the design process of eHealth interventions to meet user values and needs. In this study, individual interviews and focus groups were conducted with people with obesity (n=23) and other key stakeholders (n=27) to explore end user values and needs related to weight loss maintenance. Design thinking methods were applied during the focus group sessions to identify design elements and to explore how eHealth solutions can support the needs to achieve sustainable weight loss maintenance. The PSD model and behavior change taxonomy by Michie were used to identify PSD principles and BCT clusters to meet end user values and needs. Results A total of 8 key end user values were identified, reflecting user needs for weight loss maintenance support: self-management, personalized care, autonomy, feel supported, positive self-image, motivation, happiness, and health. Goals and planning, feedback and monitoring, repetition and substitution, shaping knowledge, social support, identity, and self-belief were some of the BCT clusters identified to address these concepts, together with PSD principles such as personalization, tailoring, self-monitoring, praise, and suggestions. Conclusions The process of translating end user values and needs into design elements or features of eHealth technologies is an important part of the design process. To our knowledge, this is the first study to explore how PSD principles and BCTs can be integrated when designing eHealth self-management interventions for long-term weight loss maintenance. End users and other key stakeholders highlighted important factors to be considered in the design of eHealth interventions supporting sustained behavior change. The PSD principles and BCTs identified provide insights and suggestions about design elements and features to include for supporting weight loss maintenance. The findings indicate that a combination of BCTs and PSD principles may be needed in evidence-based eHealth interventions to stimulate motivation and adherence to support healthy behaviors and sustained weight loss maintenance. Trial Registration ClinicalTrials.gov NCT04537988; https://clinicaltrials.gov/ct2/show/NCT04537988

• Hjelmesæth, Jøran; Hertel, Jens Kristoffer; Holt, Ane Hjetland; Benestad, Beate; Seeberg, Lars Thomas & Lindberg, Morten [Show all 10 contributors for this article] (2020). Laparoskopisk gastrisk bypassoperasjon versus livsstilsbehandling av unge med sykelig overvekt. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.20.0526. Full text in Research Archive Show summary

  BAKGRUNN Kunnskapsgrunnlaget om effekten av og komplikasjoner ved vektreduserende kirurgi hos ungdom er mangelfullt. Hovedformålet med 4XL-studien er å avklare om laparoskopisk Roux-en-Y gastrisk bypassoperasjon (LGBP) kombinert med livsstilsintervensjon er en sikker og effektiv behandlingsmetode. MATERIALE OG METODE Materialet er hentet fra en pågående ikke-randomisert intervensjonsstudie av ungdom med sykelig overvekt, der man sammenlikner effektene av gastrisk bypass kombinert med livsstilsintervensjon og livsstilsintervensjon alene. RESULTATER Totalt 39 pasienter (64 % jenter) behandlet med gastrisk bypass og 96 pasienter (57 % jenter) behandlet med livsstilsintervensjon ble undersøkt før og ett år etter behandlingsstart. Ved inklusjon var gjennomsnittsalderen (SD) hhv. 16,7 år (1,0) vs. 15,6 år (1,3), og gjennomsnittlig BMI 45,6 kg/m2 (4,4) vs. 43,3 kg/m2 (4,1) i de to gruppene. Gjennomsnittlig prosentuelt vekttap var 30 % (95 % KI 27 til 33) etter kirurgi versus en vektøkning på 1 % (95 % KI −1 til 3) i kontrollgruppen. Forskjellen mellom gruppene var 31 % (95 % KI 27 til 34, p < 0,001). Kardiometabolske risikofaktorer bedret seg kun etter kirurgi. Etter gastrisk bypass ble det registrert to tidlige (< 6 uker) mindre alvorlige komplikasjoner. Ett år etter kirurgi hadde totalt 4 (10 %) pasienter anemi, 8 (21 %) jernmangel og 4 (10 %) lave vitamin B12-verdier. 20 av 33 testede (61 %) pasienter hadde lavt totimers-blodsukker (< 2,8 mmol/L) etter glukosebelastning. FORTOLKNING Resultatene støtter tidligere studier som har vist at gastrisk bypass er assosiert med betydelig vektreduksjon hos unge pasienter med sykelig overvekt. 4XL-studien er foreløpig for liten og oppfølgingstiden for kort til å kunne vurdere risikoen for langtidskomplikasjoner.

• Wegler, Christine; Ölander, Magnus; Wisniewski, JR; Lundquist, Patrick; Zettl, K & Åsberg, Anders [Show all 9 contributors for this article] (2020). Global variability analysis of mRNA and protein concentrations across and within human tissues. NAR Genomics and Bioinformatics. 2(1), p. 1–11. doi: 10.1093/nargab/lqz010. Full text in Research Archive Show summary

  Abstract Genes and proteins show variable expression patterns throughout the human body. However, it is not clear whether relative differences in mRNA concentrations are retained on the protein level. Furthermore, inter-individual protein concentration variability within single tissue types has not been comprehensively explored. Here, we used the Gini index for in-depth concentration variability analysis of publicly available transcriptomics and proteomics data, and of an in-house proteomics dataset of human liver and jejunum from 38 donors. We found that the transfer of concentration variability from mRNA to protein is limited, that established ‘reference genes’ for data normalization vary markedly at the protein level, that protein concentrations cover a wide variability spectrum within single tissue types, and that concentration variability analysis can be a convenient starting point for identifying disease-associated proteins and novel biomarkers. Our results emphasize the importance of considering individual concentration levels, as opposed to population averages, for personalized systems biology analysis.

• Lund, Randi Størdal; Hertel, Jens Kristoffer; Sandbu, Rune & Hjelmesæth, Jøran (2020). Patient complaints following bariatric surgery 2012-18. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.20.0194. Full text in Research Archive Show summary

  BAKGRUNN Vi undersøkte saker fremmet for Norsk pasientskadeerstatning (NPE) etter vektreduserende kirurgi, inkludert bakgrunnen for klagen, andel pasienter som fikk medhold, og kjennetegn ved saker der klager fikk medhold. MATERIALE OG METODE Samtlige klagesaker knyttet til vektreduserende kirurgisk behandling i perioden 2012–18 ble gjennomgått og kategorisert med henblikk på symptomer, funn og hendelser med relevans for utfallet av klagesaken. Anonyme resyméer fra de sakkyndiges uttalelser ble gjennomgått og kategorisert etter årstall for vedtak, kjønn, alder, grunnlag for medhold eller avslag på erstatning samt hvorvidt behandlingen var utført i offentlig eller privat regi. RESULTATER Det ble gitt medhold i 44 (26 %) av totalt 171 søknader om pasientskadeerstatning. Disse søknadene kom fra 25 pasienter som var operert i det offentlige (19 % medhold) og 19 pasienter operert i det private helsevesenet (51 % medhold). Den hyppigste enkeltårsaken til medhold (n = 18) var manglende indikasjon for vektreduserende operasjon. FORTOLKNING Manglende indikasjon utløste medhold i flere klagesaker etter vektreduserende kirurgi enn kirurgtekniske feil. Riktig pasientutvelgelse, god preoperativ forberedelse, god informasjon og samvalg er viktig for best mulig resultat av vektreduserende kirurgi. Et tverrfaglig team som følger pasientene over tid, kan bidra til å kvalitetssikre hele behandlingskjeden.

• Lorentzen, Jolanta Halabowska; Medhus, Asle Wilhelm; Hertel, Jens Kristoffer; Borgeraas, Heidi; Karlsen, Tor-Ivar & Kolotkin, Ronette Loganzo [Show all 12 contributors for this article] (2020). Erosive Esophagitis and Symptoms of Gastroesophageal Reflux Disease in Patients with Morbid Obesity with and without Type 2 Diabetes: a Cross-sectional Study. Obesity Surgery. ISSN 0960-8923. 30, p. 2667–2675. doi: 10.1007/s11695-020-04545-w. Full text in Research Archive Show summary

  Background 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. Methods 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. Results 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 (< 29%) and did not differ significantly between groups, while the proportions of patients with esophagitis were high both in the T2DM and non-T2DM group, 58% versus 47%, p = 0.16. The majority of patients with esophagitis did not have GERD-symptoms (68–80%). Further, 55% of the patients with T2DM had pathologic acid reflux. Among these, 71% also had erosive esophagitis, whereof 67% were asymptomatic. Conclusions The prevalence of GERD was similar in bariatric patients with or without T2DM, and the proportion of patients with asymptomatic GERD was high independent of the presence or absence of T2DM. Accordingly, GERD may be underdiagnosed in patients not undergoing a preoperative endoscopy or acid reflux assessment

• Aakre, Kristin Moberg; Omland, Torbjørn; Nordstrand, Njord; Gjevestad, Espen Svendsen; Holven, Kirsten Bjørklund & Lyngbakken, Magnus [Show all 7 contributors for this article] (2020). Gastric bypass surgery is associated with reduced subclinical myocardial injury and greater activation of the cardiac natriuretic peptide system than lifestyle intervention. Clinical Biochemistry. ISSN 0009-9120. 86, p. 36–44. doi: 10.1016/j.clinbiochem.2020.09.006. Full text in Research Archive Show summary

  Aims Morbid obesity is a risk factor for cardiovascular disease. The relative effects of Roux-en-Y gastric bypass surgery (GBS) and intensive lifestyle intervention (ILI) on subclinical myocardial injury, the activity of the cardiac natriuretic system, and systemic inflammation remain unclear. Methods In a 59-week non-randomized clinical trial that included 131 patients with morbid obesity, we compared the effects of GBS and ILI on concentrations of cardiac troponin T (cTnT) and I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP). Results In the GBS and ILI group, median body mass index (BMI) was reduced by 14.4 kg/m2 versus 3.9 kg/m2, respectively (p value < 0.001). Cardiac troponins decreased after GBS, p = 0.014 (cTnT) and p = 0.065 (cTnI) and increased significantly in those treated with ILI (p values ≤ 0.021) (between-group differences for deltas: p ≤ 0.003). NT-proBNP increased in both groups, but significantly more in the GBS than in the ILI group (between-group differences for deltas: p = 0.008). CRP decreased significantly within the GBS and the ILI group, with this change significantly greater in the GBS group (between-group differences for deltas p < 0.001). The dominating mediator of the biomarker changes was weight loss. Prior coronary artery disease and diabetes were predictive of the magnitude of the changes in cTnI and NT-proBNP, respectively. Conclusion Compared to ILI, GBS was associated with reduced subclinical myocardial injury and systemic inflammation, and enhancement of the cardiac natriuretic peptide system. The biomarker changes were predominantly mediated by weight loss.

• Wegler, Christine; Garcia, Luna Prieto; Klinting, Signe; Robertsen, Ida; Wisniewski, Jacek R. & Hjelmesæth, Jøran [Show all 10 contributors for this article] (2020). Proteomics‐informed prediction of rosuvastatin plasma profiles in patients with a wide range of body weight. Clinical Pharmacology and Therapeutics. ISSN 0009-9236. 109(3), p. 762–771. doi: 10.1002/cpt.2056. Full text in Research Archive
• Løkling, Hanne Lund; Roelants, Mathieu; Kommedal, Kristin Garpestad; Skjåkødegård, Hanna Flækøy; Apalset, Ellen M & Benestad, Beate [Show all 9 contributors for this article] (2019). Monitoring children and adolescents with severe obesity: body mass index (BMI), BMI z-score or percentage above the International Obesity Task Force overweight cut-off? Acta Paediatrica. ISSN 0803-5253. 108(12), p. 2261–2266. doi: 10.1111/apa.14898. Full text in Research Archive Show summary

  Aim: Body mass index (BMI) metrics are widely used as a proxy for adiposity in children with severe obesity. The BMI expressed as the percentage of a cut‐off percentile for overweight or obesity has been proposed as a better alternative than BMI z‐scores when monitoring children and adolescents with severe obesity. Methods: Annual changes in BMI, BMI z‐score and the percentage above the International Obesity Task Force overweight cut‐off (%IOTF‐25) were compared with dual‐energy X‐ray absorptiometry (DXA) derived body fat (%BF‐DXA) in 59 children and adolescents with severe obesity. Results: The change in %BF‐DXA was correlated with the change in %IOTF‐25 (r = 0.68) and BMI (r = 0.70), and somewhat less with the BMI z‐score (r = 0.57). Cohen's Kappa statistic to detect an increase or decrease in %BF‐DXA was fair for %IOTF‐25 (κ = 0.25; p = 0.04) and BMI (κ = 0.33; p = 0.01), but not for the BMI z‐score (κ = 0.08; p = 0.5). The change in BMI was positively biased due to a natural increase with age. Conclusion: Changes in the BMI metrics included in the study are associated differently with changes in %BF‐DXA. The BMI z‐score is widely used to monitor changes in adiposity in children and adolescents with severe obesity, but the %IOTF‐25 might be a better alternative.

• Borgeraas, Heidi; Hjelmesæth, Jøran; Birkeland, Kåre I.; Fatima, Farhat; Grimnes, John Olav & Gulseth, Hanne Løvdal [Show all 22 contributors for this article] (2019). Single-centre, triple-blinded, randomised, 1-year, parallel-group, superiority study to compare the effects of Roux-en-Y gastric bypass and sleeve gastrectomy on remission of type 2 diabetes and β-cell function in subjects with morbid obesity: a protocol for the Obesity surgery in Tønsberg (Oseberg) study. BMJ Open. 9(6). doi: 10.1136/bmjopen-2018-024573. Full text in Research Archive Show summary

  Introduction Bariatric surgery is increasingly recognised as an effective treatment option for subjects with type 2 diabetes and obesity; however, there is no conclusive evidence on the superiority of Roux-en-Y gastric bypass or sleeve gastrectomy. The Oseberg study was designed to compare the effects of gastric bypass and sleeve gastrectomy on remission of type 2 diabetes and β-cell function. Methods and analysis Single-centre, randomised, triple-blinded, two-armed superiority trial carried out at the Morbid Obesity Centre at Vestfold Hospital Trust in Norway. Eligible patients with type 2 diabetes and obesity were randomly allocated in a 1:1 ratio to either gastric bypass or sleeve gastrectomy. The primary outcome measures are (1) the proportion of participants with complete remission of type 2 diabetes (HbA1c≤6.0% in the absence of blood glucose-lowering pharmacologic therapy) and (2) β-cell function expressed by the disposition index (calculated using the frequently sampled intravenous glucose tolerance test with minimal model analysis) 1 year after surgery. Ethics and dissemination The protocol of the current study was reviewed and approved by the regional ethics committee on 12 September 2012 (ref: 2012/1427/REK sør-øst B). The results will be disseminated to academic and health professional audiences and the public via publications in international peer-reviewed journals and conferences. Participants will receive a summary of the main findings. Trial registration number NCT01778738;Pre-results. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial

• Svanevik, Marius; Risstad, Hilde; Hofsø, Dag; Høgestøl, Ingvild Kristine; Kristinsson, Jon Adalsteinn & Sandbu, Rune [Show all 10 contributors for this article] (2019). Bone Turnover Markers After Standard and Distal Roux-en-Y Gastric Bypass: Results from a Randomized Controlled Trial. Obesity Surgery. ISSN 0960-8923. 29(9), p. 2886–2895. doi: 10.1007/s11695-019-03909-1. Full text in Research Archive Show summary

  Background: Roux-en-Y gastric bypass is associated with increased risk of bone fractures. Malabsorptive procedures may be associated with secondary hyperparathyroidism and detrimental effects on bone health. We aimed to compare the effects of standard and distal gastric bypass on bone turnover markers 2 years after surgery. Methods: Patients with body mass index (BMI) 50–60kg/m2 (n=113) were randomized to standard or distal gastric bypass,105 patients (95%) completed 2-year follow-up. Serum C-terminal telopeptide of type I collagen (CTX-1), procollagen type I Npropeptide (PINP), and bone-derived alkaline phosphatase (BALP) was measured at baseline and up to 2 years after surgery. ANCOVA and linear mixed models were used to compare groups. Results: The levels of bone turnover markers increased significantly in both groups, with no statistically significant difference betweengroups.Two years after standard and distal gastric bypass mean (SD) CTX-1 were 0.81 (0.32) and 0.83 (0.31) μg/L (p= 0.38), mean PINP was 77.6 (23.2) and 77.7 (29.3) μg/L (p=0.42), and BALP 47.9 (21.9) vs. 50.7 (19.6) μg/L (p=0.38), respectively. Multiple linear regression analyses showed that PINP and BALP correlated positively (p=0.01 and p <0.001) with PTH, but only BALP was significantly higher in patients with secondary hyperparathyroidism (p=0.001). Type of surgery, vitamin D serum concentrations, and 2-year BMI were all independently associated with PTH levels. Conclusion: A comparable increase in bone turnover markers 2 years after standard and distal gastric bypass was observed. There was a higher prevalence of secondary hyperparathyroidism after distal gastric bypass, but this did not impact bone turnover markers.

• Benestad, Beate; Karlsen, Tor-Ivar; Småstuen, Milada Cvancarova; Lekhal, Samira; Hertel, Jens Kristoffer & Steinsbekk, Silje [Show all 9 contributors for this article] (2019). Health-related quality of life after camp-based family obesity treatment: an RCT. BMJ Paediatrics Open. 3(1). doi: 10.1136/bmjpo-2018-000413. Full text in Research Archive Show summary

  Objective To 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. Design Randomised controlled trial. Setting Rehabilitation clinic, tertiary care hospital and primary care. Patients Families with at least one child (7–12 years) and one parent, both with obesity. Interventions Summer 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 measures Children’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. Results Ninety 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. Conclusions A 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.

• Krogstad, Veronica; Peric, Alexandra; Robertsen, Ida; Kringen, Marianne K.; Wegler, Christine & Angeles, Philip Carlo Soriano [Show all 13 contributors for this article] (2019). A Comparative Analysis of Cytochrome P450 Activities in Paired Liver and Small Intestinal Samples from Patients with Obesity. Drug Metabolism And Disposition. ISSN 0090-9556. 48(1), p. 8–17. doi: 10.1124/DMD.119.087940. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Smedsrød, Mirjam Lien; Nes, Lise Solberg; Wentzel, Jobke; Varsi, Cecilie & Hjelmesæth, Jøran [Show all 7 contributors for this article] (2019). Persuasive system design principles and behavior change techniques to stimulate motivation and adherence in electronic health interventions to support weight loss maintenance: Scoping review. Journal of Medical Internet Research (JMIR). ISSN 1439-4456. 21(6). doi: 10.2196/14265. Full text in Research Archive Show summary

  Background: Maintaining weight after weight loss is a major health challenge, and eHealth (electronic health) solutions may be a way to meet this challenge. Application of behavior change techniques (BCTs) and persuasive system design (PSD) principles in eHealth development may contribute to the design of technologies that positively influence behavior and motivation to support the sustainable health behavior change needed. Objective: This review aimed to identify BCTs and PSD principles applied in eHealth interventions to support weight loss and weight loss maintenance, as well as techniques and principles applied to stimulate motivation and adherence for long-term weight loss maintenance. Methods: A systematic literature search was conducted in PsycINFO, Ovid MEDLINE (including PubMed), EMBASE, Scopus, Web of Science, and AMED, from January 1, 2007 to June 30, 2018. Arksey and O’Malley’s scoping review methodology was applied. Publications on eHealth interventions were included if focusing on weight loss or weight loss maintenance, in combination with motivation or adherence and behavior change. Results: The search identified 317 publications, of which 45 met the inclusion criteria. Of the 45 publications, 11 (24%) focused on weight loss maintenance, and 34 (76%) focused on weight loss. Mobile phones were the most frequently used technology (28/45, 62%). Frequently used wearables were activity trackers (14/45, 31%), as well as other monitoring technologies such as wireless or digital scales (8/45, 18%). All included publications were anchored in behavior change theories. Feedback and monitoring and goals and planning were core behavior change technique clusters applied in the majority of included publications. Social support and associations through prompts and cues to support and maintain new habits were more frequently used in weight loss maintenance than weight loss interventions. In both types of interventions, frequently applied persuasive principles were self-monitoring, goal setting, and feedback. Tailoring, reminders, personalization, and rewards were additional principles frequently applied in weight loss maintenance interventions. Results did not reveal an ideal combination of techniques or principles to stimulate motivation, adherence, and weight loss maintenance. However, the most frequently mentioned individual techniques and principles applied to stimulate motivation were, personalization, simulation, praise, and feedback, whereas associations were frequently mentioned to stimulate adherence. eHealth interventions that found significant effects for weight loss maintenance all applied self-monitoring, feedback, goal setting, and shaping knowledge, combined with a human social support component to support healthy behaviors. Conclusions: To our knowledge, this is the first review examining key BCTs and PSD principles applied in weight loss maintenance interventions compared with those of weight loss interventions. This review identified several techniques and principles applied to stimulate motivation and adherence. Future research should aim to examine which eHealth design combinations can be the most effective in support of long-term behavior change and weight loss maintenance.

• Berge, Jarle; Støren, Øyvind; Hertel, Jens Kristoffer; Gjevestad, Espen Svendsen; Småstuen, Milada Cvancarova & Hjelmesæth, Jøran (2019). Associations between cardiorespiratory fitness and weight loss in patients with severe obesity undergoing an intensive lifestyle intervention program: retrospective cohort study. BMC Endocrine Disorders. 19(1), p. 1–9. doi: 10.1186/s12902-019-0394-z. Full text in Research Archive Show summary

  Background To assess the association between cardiorespiratory fitness (CRF) and weight changes in treatment seeking patients with severe obesity who underwent a 1-year intensive lifestyle intervention (ILI) program. Methods Retrospective cohort study conducted at a tertiary care outpatient rehabilitation center from November 1, 2013 through January 1, 2017. CRF was measured as maximal oxygen consumption during a maximal oxygen uptake (VO2max) test on a treadmill or bicycle at baseline and after 3 months. Results A total of 180 patients had a baseline mean (SD) BMI 41.1 (4.8) kg/m2 and CRF of 79.4 (14.9) mL·kg-0.75·min− 1. Patients with a baseline CRF above median achieved a greater 3-month and 1-year weight loss compared with patients with CRF below median; mean (95% CI) 2.5 kg (1.3, 3.8) and 4.0 kg (0.8, 7.2), respectively. In addition, patients with 3-month changes of CRF above median had 4.0 kg (0.9, 7.1) greater weight loss at 1-year follow-up than those below median. Conclusions Among patients with severe obesity who underwent a 1-year ILI program, higher baseline CRF was associated with significantly larger weight loss after 3 months and 1 year. In addition, those with higher initial 3-month CRF changes had greater weight loss at 1 year.

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• Asbjørnsen, Rikke Aune; Hjelmesæth, Jøran Sture; Ollivier, Marianne; Johnson, Line Kristin; Hertel, Jens Kristoffer & Nes, Lise Solberg (2026). Initiating the eBATTLE Obesity Project: User-Centered Design of a Digital Intervention to Support Healthy Lifestyle and Weight Management in Adolescents with Obesity. doi: 10.1093/abm/kaag012. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Børøsund, Elin; Hjelmesæth, Jøran Sture; Smedsrød, Mirjam Lien; Ollivier, Marianne & Wentzel, Jobke [Show all 9 contributors for this article] (2025). Approaches from idea to implementation of eHealth innovations in healthcare: Experiences and perspectives from an eHealth innovation seeking to support behavior change after weight loss. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Børøsund, Elin; Hjelmesæth, Jøran Sture; Smedsrød, Mirjam Lien; Ollivier, Marianne & Clark, Matthew [Show all 9 contributors for this article] (2024). System Use Findings from a Pilot Trial with the Digital Weight Loss Maintenance Intervention eCHANGE. Full text in Research Archive
• Ollivier, Marianne; Søiland, Nora Bergem; Hertel, Jens Kristoffer; Hjelmesæth, Jøran Sture; Asbjørnsen, Rikke Aune & Johnson, Line Kristin [Show all 7 contributors for this article] (2024). Presentasjon av Habition. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Børøsund, Elin; Hjelmesæth, Jøran Sture; Ollivier, Marianne; Smedsrød, Mirjam Lien & Wentzel, Jobke [Show all 9 contributors for this article] (2023). Long-term Weight Maintenance After Weight Loss: Preliminary Findings from the eCHANGE Pilot Trial. Full text in Research Archive Show summary

  Annals of Behavioral Medicine, Volume 57, Issue Supplement_1, April 2023

• Asbjørnsen, Rikke Aune; Børøsund, Elin; Hjelmesæth, Jøran Sture; Smedsrød, Mirjam Lien; Ollivier, Marianne & Wentzel, Jobke [Show all 8 contributors for this article] (2023). Engaging with eCHANGE - Users’ Experiences with an App-based Weight Loss Maintenance Intervention: A Pilot-Trial. Full text in Research Archive
• Pfabigan, Daniela Melitta; Hertel, Jens Kristoffer; Svanevik, Marius; Lindberg, Morten; Sailer, Uta & Hjelmesæth, Jøran Sture (2023). Single-centre, non-randomised clinical trial at a tertiary care centre to investigate 1-year changes in social experiences and biomarkers of well-being after bariatric surgery in individuals with severe obesity: protocol for the Bariatric Surgery and Social Experiences (BaSES) study. BMJ open gastroenterology. doi: 10.1136/bmjopen-2022-071332. Full text in Research Archive Show summary

  Introduction Obesity is linked to increased loneliness and less enjoyment of social interactions. While bariatric surgery is the most effective treatment targeting severe obesity, there is limited understanding as to whether patients experience social interactions differently after surgery. The Bariatric Surgery and Social Experiences study is designed to assess potential changes in how much patients enjoy and engage in daily social interactions 1 year after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Methods and analysis Single-centre, non-randomised clinical trial carried out at the Department of Endocrinology, Obesity and Nutrition at Vestfold Hospital Trust, Norway. Eligible patients (N=113) will undergo either RYGB, SG or single anastomosis sleeve ileal (SASI) bypass. The primary outcome measure is change in the social experience score (assessed with a questionnaire) from a presurgery to a follow-up assessment 1 year after RYGB and SG. The respective changes after SASI bypass will be assessed and considered exploratory. Ethics and dissemination The most recent protocol version of this study was reviewed and approved by the Regional Committee for Medical Research Ethics South East Norway (REK sør-øst A) on 29 August 2022 (ref: 238406). The results will be disseminated to academic and health professional audiences and the public via publications in international peer-reviewed journals and conferences.

• Hjelmesæth, Jøran Sture; Torheim, Liv Elin & Arnesen, Erik Kristoffer (2023). Hva kreves av kunnskap før man gir kostholdsråd? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(11). doi: 10.4045/tidsskr.23.0451. Full text in Research Archive
• Ødegård, Rønnaug Astri; Juliusson, Pétur Benedikt; Kokkvoll, Ane Sofie; Kristiansen, Hege; Köpp, Unni Mette Stamnes & Rolin, Johannes [Show all 9 contributors for this article] (2023). Ungdom med alvorlig fedme bør få legemiddel på blå resept. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(3), p. 1–4. doi: 10.4045/tidsskr.23.0069. Full text in Research Archive
• Hjelmesæth, Jøran Sture; Torheim, Live Elin & Arnesen, Erik Kristoffer (2023). J. Hjelmesæth og medarbeidere svarer. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 143(13). doi: 10.4045/tidsskr.23.0589. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Ollivier, Marianne; Smedsrød, Mirjam Lien; Hjelmesæth, Jøran Sture; Wentzel, Jobke & Clark, Matthew M. [Show all 8 contributors for this article] (2022). Design Features for Long Term Weight Loss Maintenance: User Experiences and Preferences from the eCHANGE Pilot Trial. Full text in Research Archive
• Lorentzen, Jolanta Halabowska; Medhus, Asle Wilhelm; Hofsø, Dag; Svanevik, Marius; Seip, Birgitte Karen Berggreen & Hjelmesæth, Jøran Sture (2022). Letter to the Editor regarding the article «Gerd symptoms after laparoscopic Roux-en-Y gastric bypass: an emerging scenario» by Antonella Santonicola, Luigi Ruggiero, Rossella Palma, Luigi Angrisani and Paola Iovino. International Journal of Obesity (2022) 46:1076–1078. International Journal of Obesity. ISSN 0307-0565. 46(10), p. 1936–1937. doi: 10.1038/s41366-022-01200-5. Full text in Research Archive
• Borgeraas, Heidi; Hofsø, Dag; Svanevik, Marius & Hjelmesæth, Jøran Sture (2022). Comment on “Effectiveness of Roux‑en‑Y Gastric Bypass vs Sleeve Gastrectomy on Lipid Levels in Type 2 Diabetes: a Meta‑analysis”. Journal of Gastrointestinal Surgery. ISSN 1091-255X. 26(9), p. 2031–2032. doi: 10.1007/s11605-022-05419-5. Full text in Research Archive
• Borgeraas, Heidi; Hofsø, Dag; Hertel, Jens Kristoffer & Hjelmesæth, Jøran Sture (2022). Addendum to: Comparison of the effect of Roux-en-Y gastric bypass and sleeve gastrectomy on remission of type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Obesity Reviews. ISSN 1467-7881. doi: 10.1111/obr.13432. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Wentzel, Jobke; Smedsrød, Mirjam Lien; Ollivier, Marianne; Hjelmesæth, Jøran & Gemert-Pijnen, Lisette Van [Show all 7 contributors for this article] (2021). Co-creating with patients and other stakeholders: design of an eHealth intervention to support long-term behavior change and weight loss maintenance (eCHANGE). Full text in Research Archive
• Barstad, Lisa Ha; Lund, Randi Størdal; Flakstad, Inger Marie; Johnson, Line Kristin; Aarvik, Andreas & Hertel, Jens Kristoffer [Show all 7 contributors for this article] (2020). Livsstilsendringskurs som fedmebehandling i spesialisthelsetjenesten - kvalitetssikring i praksis. Norsk tidsskrift for ernæring (NTFE). ISSN 1503-5034. Full text in Research Archive
• Hjelmesæth, Jøran; Fatima, Farhat; Birkeland, Kåre I.; Svanevik, Marius & Hofsø, Dag (2020). Metabolic surgery: one size fits all? - Authors' reply. The Lancet Diabetes and Endocrinology. ISSN 2213-8587. 8, p. 273–273. doi: 10.1016/S2213-8587(20)30027-9. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Wentzel, Jobke; Smedsrød, Mirjam Lien; Hjelmesæth, Jøran; Clark, Matthew & Gemert-Pijnen, Lisette Van [Show all 7 contributors for this article] (2020). Personalized eHealth technology for weight maintenance and long term behavior change. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Smedsrød, Mirjam Lien; Hjelmesæth, Jøran; Hertel, Jens Kristoffer; Wentzel, Jobke & Johnson, Line Kristin [Show all 15 contributors for this article] (2020). eHealth design: Which persuasive and behavior change techniques meet the user needs for weight maintenance support? Full text in Research Archive Show summary

  Conference Theme: Finding Innovative Solutions for Tomorrow's Health Challenges

• Mathisen, Therese Fostervold; Sundfør, Tine Mejlbo; Hjelmesæth, Jøran; Kaalstad, Jørn E. & Arnesen, Erik Kristoffer (2020). 5 eksperter: Slik holder du vekten nede. [Internet]. Vg.no. Full text in Research Archive
• Hjelmesæth, Jøran & Hertel, Jens Kristoffer (2020). Kommentar til "Den kvasse samtalen". Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. doi: 10.4045/tidsskr.20.0199. Full text in Research Archive
• Borgeraas, Heidi; Hofsø, Dag & Hjelmesæth, Jøran (2020). Comment on "Laparoscopic Sleeve Gastrectomy Versus Laparoscopic Roux-en-Y Gastric Bypass: A Systematic Review and Meta-analysis of Weight Loss, Comorbidities, and Biochemical Outcomes From Randomized Controlled Trials". Annals of Surgery. ISSN 0003-4932. 274(6). doi: 10.1097/SLA.0000000000003899. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Wentzel, Jobke; Smedsrød, Mirjam Lien; Ollivier, Marianne; Hjelmesæth, Jøran & Gemert-Pijnen, Lisette Van [Show all 7 contributors for this article] (2020). Co-creating with patients and other stakeholders: Design of an eHealth intervention to support long-term behavior change and weight loss maintenance. Full text in Research Archive
• Svanevik, Marius; Salte, Odd Bjørn; Risstad, Hilde; Hjelmesæth, Jøran; Høgestøl, Ingvild Kristine & Hertel, Jens Kristoffer [Show all 10 contributors for this article] (2019). BMI loss and resolution of diabetes five years after standard and distal roux-en-y gastric bypass. Surgery for Obesity and Related Diseases. ISSN 1550-7289. 15, p. S115–S115. doi: 10.1016/j.soard.2019.08.234. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Smedsrød, Mirjam Lien; Hjelmesæth, Jøran; Hertel, Jens Kristoffer; Gemert-Pijnen, Lisette Van & Varsi, Cecilie [Show all 21 contributors for this article] (2019). Building an eHealth intervention for weight maintenance after weight loss: Identifying behavioral design elements & user needs. Full text in Research Archive
• Johnson, Line Kristin; Sandbu, Rune; Robertsen, Ida; Åsberg, Anders; Andersson, Tommy & Andersson, Shalini [Show all 8 contributors for this article] (2019). Effect of gastric bypass and very-low energy diet on cardiometabolic risk factors. Surgery for Obesity and Related Diseases. ISSN 1550-7289. 15, p. S114–S114. doi: 10.1016/j.soard.2019.08.232. Full text in Research Archive
• Angeles, Philip Carlo Soriano; Robertsen, Ida; Seeberg, Lars Thomas; Krogstad, Veronica; Sandbu, Rune & Åsberg, Anders [Show all 7 contributors for this article] (2019). Reply to letter: “What about drug bioavailability in patients who had bariatric surgery and dependent on immunosuppressives?”. Obesity Reviews. ISSN 1467-7881. 21(2). doi: 10.1111/obr.12954. Full text in Research Archive
• Skaug, Therese Doksheim; Mathisen, Therese Fostervold; Hjelmesæth, Jøran & Svihus, Birger (2019). Unngå magefett-fellene. [Journal]. Dagbladet. Full text in Research Archive
• Seeberg, Kathrine; Borgeraas, Heidi; Hertel, Jens Kristoffer; Grimnes, John Olav; Kvan, Nils Petter & Fatima, Farhat [Show all 10 contributors for this article] (2019). Gastric bypass and sleeve gastrectomy for hepatic steatosis in type 2 diabetes – a randomized controlled trial. Surgery for Obesity and Related Diseases. ISSN 1550-7289. 15, p. S27–S28. doi: 10.1016/j.soard.2019.08.085. Full text in Research Archive
• Mathisen, Therese Fostervold; Hjelmesæth, Jøran & Westeng, Kjersti (2019). Følger du «CICO-dietten», går du ned i vekt. Men ekspertene advarer klart mot å gjøre det. [Internet]. Nettavisen. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Smedsrød, Mirjam Lien; Nes, Lise Solberg; Wentzel, Jobke; Varsi, Cecilie & Hjelmesæth, Jøran [Show all 7 contributors for this article] (2019). Weight maintenance: Finding effective combinations of persuasive and behavior change techniques stimulating motivation and adherence. Full text in Research Archive Show summary

  Obesity and weight-loss maintenance (WM) is a major health challenge that requires novel solutions, as three out of four regain lost weight. Combining persuasive design principles (PSDs) with behavior change techniques(BCTs) in eHealth development could contribute to facilitate the behavior change needed.

• Lorentzen, Jolanta Halabowska; Medhus, Asle Wilhelm; Hertel, Jens Kristoffer; Karlsen, Tor-Ivar; Borgeraas, Heidi & Sandbu, Rune [Show all 10 contributors for this article] (2019). Gastroesophageal reflux disease in patients With severe obesity and type 2 diabetes one year after sleeve gastrectomy or roux-en-y gastric bypass. A Randomized controlled trial. Surgery for Obesity and Related Diseases. ISSN 1550-7289. 15, p. S3–S3. doi: 10.1016/j.soard.2019.08.052. Full text in Research Archive
• Asbjørnsen, Rikke Aune; Smedsrød, Mirjam Lien; Hjelmesæth, Jøran; Hertel, Jens Kristoffer; Gemert-Pijnen, Lisette Van & Varsi, Cecilie [Show all 23 contributors for this article] (2019). eCHANGE - E-helseverktøy for å støtte opp om langvarig vedlikehold av vekttap. Full text in Research Archive
• Arnesen, Erik Kristoffer; Hjelmesæth, Jøran Sture; Torheim, Liv Elin; Holven, Kirsten Bjørklund; Mortensen, Kari Hege & Korsæth, Audun (2021). Ekspertuttalelse om fett fra Nasjonalt råd for ernæring. Helsedirektoratet. Full text in Research Archive

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