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Purpose: Obesity may alter the severity of infection with Coronavirus disease 2019 (COVID-19). Age may impact the association between body weight and severity of COVID-19 in patients with obesity. The aim of the study was to examine the association between obesity and severity of infection in a Danish cohort hospitalized with COVID-19 in the initial wave of the pandemic. Patients and methods: Based on data from the nationwide, clinical database: COVID-DK, risks of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), and mortality were compared among patients with and without obesity. Interaction with age was examined and we used Inverse Probability of Treatment Weighting regression for confounder adjustment. Results: Among 524 patients, 142 (27%) were admitted to the ICU, 112 (21%) required IMV, and 109 (21%) died. Compared to COVID-19 patients without obesity, patients with obesity displayed a non-significant increased risk of ICU admission (Relative Risk [RR] 1.19, 95% Confidence Interval [CI] 0.88; 1.60), IMV (RR 1.23, CI 0.86; 1.75) and mortality (RR 1.21, CI 0.84; 1.75). COVID-19 patients with obesity, <60 years had highly increased risk of ICU admission (RR 1.92, CI 1.14; 3.24) and IMV (RR 1.95, CI 1.09; 3.49). Conclusions: In hospitalized COVID-19 patients, obesity conferred an approximately 20% increased risk for ICU admission, IMV, and death, although these relationships did not reach statistical significance. COVID-19 patients with obesity and <60 years had an almost doubled risk of ICU admission and IMV.

Aim Weight bias, stigma and discrimination are pervasive in the health care system and society and may result in biased treatment of people living with obesity (PwO). We aimed to identify perceptions, attitudes and potential barriers that exist between people with obesity and health care professionals (HCPs) in Denmark. Methods The ACTION-DK survey was a cross-sectional, non-interventional, descriptive study conducted in Denmark. The cohort included 879 PwO (body mass index ≥30.0 kg/m2) based on self-reported height and body weight, and 100 HCPs from the primary and secondary sectors who frequently encountered PwO. Results Several discrepancies between PwO and HCPs were identified, including recognition of obesity as a chronic disease (PwO: 49% vs. HCPs: 84%) and whether PwO were responsible for their weight loss (PwO: 81% vs. HCPs: 17%). Among PwO, 46% were motivated to lose weight, but only 28% of HCPs shared this perception. Untimely initiation of obesity care consultations was also identified as a potential barrier to proper obesity care, as PwO waited 7 years, on average, from their initial decision to lose weight before having their first obesity care consultation. In addition, only 24% of PwO had a follow-up consultation after the initial obesity care discussion. Almost half of HCPs (46%) considered weight loss medication effective, but only 10% brought up this possibility during an obesity care discussion. Conclusions Our findings suggest that it is pivotal to improve obesity care in Denmark by ensuring a better follow-up and alignment of the perceptions and attitudes toward obesity between PwO and HCPs., Aim: Weight bias, stigma and discrimination are pervasive in the health care system and society and may result in biased treatment of people living with obesity (PwO). We aimed to identify perceptions, attitudes and potential barriers that exist between people with obesity and health care professionals (HCPs) in Denmark. Methods: The ACTION-DK survey was a cross-sectional, non-interventional, descriptive study conducted in Denmark. The cohort included 879 PwO (body mass index ≥30.0 kg/m2) based on self-reported height and body weight, and 100 HCPs from the primary and secondary sectors who frequently encountered PwO. Results: Several discrepancies between PwO and HCPs were identified, including recognition of obesity as a chronic disease (PwO: 49% vs. HCPs: 84%) and whether PwO were responsible for their weight loss (PwO: 81% vs. HCPs: 17%). Among PwO, 46% were motivated to lose weight, but only 28% of HCPs shared this perception. Untimely initiation of obesity care consultations was also identified as a potential barrier to proper obesity care, as PwO waited 7 years, on average, from their initial decision to lose weight before having their first obesity care consultation. In addition, only 24% of PwO had a follow-up consultation after the initial obesity care discussion. Almost half of HCPs (46%) considered weight loss medication effective, but only 10% brought up this possibility during an obesity care discussion. Conclusions: Our findings suggest that it is pivotal to improve obesity care in Denmark by ensuring a better follow-up and alignment of the perceptions and attitudes toward obesity between PwO and HCPs.

Sigrid Bjerge Gribsholt,1,2 Dóra Körmendiné Farkas,3 Reimar Wernich Thomsen,3 Bjørn Richelsen,1,2 Henrik Toft Sørensen3 1Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Steno Diabetes Center, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, DenmarkCorrespondence: Sigrid Bjerge Gribsholt, Tel +4561651148, Email sigrid.bjerge.gribsholt@clin.au.dkPurpose: Data on long-term mortality among patients with hospital-diagnosed overweight/obesity are limited. Thus, we aim to examine 40-year mortality among patients with hospital-diagnosed overweight/obesity, including cause-specific deaths, secular time trends, and potential effect modification by age, comorbidity, and socioeconomic factors.Patients and Methods: From national registries, we identified all Danes with a first hospital-based overweight/obesity diagnosis (N=331,185), 1979– 2018, and constructed an age- and gender-matched general population comparison cohort (N=1,655,925). We computed mortality rates (MRs) per 1000 person-years and adjusted mortality rate ratios (aMRRs) with 95% confidence intervals (CIs), using Cox regression with adjustment for comorbidities and educational level. We performed stratified analyses on age, comorbidities, and socioeconomic factors.Results: The overall aMRR was 1.70 (95% CI: 1.68– 1.72) for patients with overweight/obesity, mainly due to diabetes and other endocrine diseases (aMRR=2.68 [95% CI: 2.57– 2.81]), cardiovascular (aMRR=1.95 [95% CI: 1.91– 1.98]), and respiratory diseases (aMRR=1.83 [95% CI: 1.77– 1.89]). The 1– 10-year aMRR decreased from 2.06 (95% CI: 2.01– 2.11) in 1979– 1989 to 1.29 (95% CI: 1.26– 1.32) in 2000– 2009. We found effect modification by age: age 18 to < 30 years: aMRR=2.44 (95% CI: 2.24– 2.66) vs age ≥ 70 years: 1.35 (95% CI: 1.33– 1.37); comorbidities: baseline comorbidities: aMRR=1.1

Background: Bariatric surgery as treatment of obesity is increasing worldwide. No guidelines exist on which type of bariatric procedure to choose for the individual patient. Objectives: This study aims to compare Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) with respect to weight loss, complications, comorbidities, and quality of life. Setting: A nationwide multi-center register-based cohort study. Methods: We identified 16,053 patients treated by bariatric surgery from 2008 to 2021 (RYGB, n = 13,075; SG, n = 2978) from the Danish quality registry for treatment of severe obesity (DBSO). We calculated risk ratios (RRs) and prevalence ratios (PRs) comparing surgical complications, weight loss, and medical comorbidities by type of procedure up to 2 years after surgery. Results: Patients treated with RYGB experienced a greater weight loss than patients treated by SG both after 1 year (PR, .53; 95% confidence interval [CI], .48–.58) and 2 years (PR, .46; 95% CI, .39–.54). Compared with RYGB, SG yielded a lower risk of readmission (RR, .71; 95% CI, .60–.85). Likewise, the risk of reoperation between 30 days and 1 year (RR, .40; 95% CI, .30–.53) and 1 and 5 years (RR, .15; 95% CI, .12–.20]) were lower following SG. At 1-year follow-up, 76% of patients treated with RYGB and 63% of patients treated with SG experienced diabetes remission. Ten percent and 61% of patients were lost to follow-up after 1 and 2 years, respectively. Conclusion: The DBSO is an important resource in studying treatment of severe obesity. Weight loss is slightly greater after RYGB than after SG, but RYGB is associated with more frequent readmissions and reoperations.

Sigrid Bjerge Gribsholt,1,2 Lars Pedersen,1 Bjørn Richelsen,3 Reimar Wernich Thomsen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 3The Steno Diabetes Centre Aarhus, Aarhus University Hospital, Aarhus, DenmarkCorrespondence: Sigrid Bjerge GribsholtDepartment of Clinical Epidemiology, Aarhus University Hospital, Olof Palmes Allé 43-45, Aarhus N 8200, DenmarkTel +45 6 165 1148Email sigrgrib@rm.dkPurpose: Health care databases may be a valuable source for epidemiological research in obesity, if diagnoses are valid. We examined the validity and completeness of International Classification of Diseases, 10th revision [ICD-10] diagnosis coding for overweight/obesity in Danish hospitals.Patients and methods: We linked data from the Danish National Patient Registry on patients with a hospital diagnosis code of overweight/obesity (ICD-10 code E66) with computerized height and weight measurements made during hospital contacts in the Central Denmark Region Clinical Information System. We computed the positive predictive value (PPV) of the IDC-10 diagnosis of overweight/obesity, using a documented body mass index (BMI) ≥25 kg/m2 as gold standard. We also examined the completeness of obesity/overweight diagnosis coding among all patients recorded with BMI ≥25 kg/m2.Results: Of all 19,672 patients registered with a first diagnosis code of overweight/obesity in the National Patient Registry, 17,351 patients (88.2%) had any BMI measurement recorded in the Central Denmark Region Clinical Information System, and 17,240 patients (87.6%) had a BMI ≥25 kg/m2, yielding a PPV of 87.6% (95% CI: 87.2–88.1). The PPV was slightly higher for primary diagnosis codes of overweight/obesity: 94.1% (95% CI: 93.3–94.8) than for secondary diagnosis codes: 86.1% (95% CI: 85.6–86.6). The PPV increas

Johnny Kahlert,1 Sigrid Bjerge Gribsholt,1,2 Henrik Gammelager,1,3 Olaf M Dekkers,1,4,5 George Luta1,6 1Department of Clinical Epidemiology, Institute of Clinical Medicine, 2Department of Endocrinology and Internal Medicine, 3Department of Anaesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark; 4Department of Clinical Epidemiology, 5Department of Medicine, Section Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; 6Department of Biostatistics, Bioinformatics, and Biomathematics, Georgetown University Medical Center, Washington, DC, USA Abstract: In observational studies, control of confounding can be done in the design and analysis phases. Using examples from large health care database studies, this article provides the clinicians with an overview of standard methods in the analysis phase, such as stratification, standardization, multivariable regression analysis and propensity score (PS) methods, together with the more advanced high-dimensional propensity score (HD-PS) method. We describe the progression from simple stratification confined to the inclusion of a few potential confounders to complex modeling procedures such as the HD-PS approach by which hundreds of potential confounders are extracted from large health care databases. Stratification and standardization assist in the understanding of the data at a detailed level, while accounting for potential confounders. Incorporating several potential confounders in the analysis typically implies the choice between multivariable analysis and PS methods. Although PS methods have gained remarkable popularity in recent years, there is an ongoing discussion on the advantages and disadvantages of PS methods as compared to those of multivariable analysis. Furthermore, the HD-PS method, despite its generous inclusion of potential confounders, is also associated with potential pitfalls. All methods are dependent on the assumption of no unknown, unmeasured and residua

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth. We describe similar massive adipose overgrowth with suppressed leptin expression in four further patients with biallelic MFN2 mutations and at least one p.Arg707Trp allele. Overgrown tissue was composed of normal-sized, UCP1-negative unilocular adipocytes, with mitochondrial network fragmentation, disorganised cristae, and increased autophagosomes. There was strong transcriptional evidence of mitochondrial stress signalling, increased protein synthesis, and suppression of signatures of cell death in affected tissue, whereas mitochondrial morphology and gene expression were normal in skin fibroblasts. These findings suggest that specific MFN2 mutations cause tissue-selective mitochondrial dysfunction with increased adipocyte proliferation and survival, confirm a novel form of excess adiposity with paradoxical suppression of leptin expression, and suggest potential targeted therapies.