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Anne Sophie Mathiesen,1 Ingrid Egerod,2 Tonny Jensen,1 Gudrun Kaldan,3 Henning Langberg,4 Thordis Thomsen3 1Department of Endocrinology, Abdominal Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 2Intensive Care Unit 4131, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 3Abdominal Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; 4CopenRehab, Section of Social Medicine, Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Abstract: Diabetes distress (DD) disproportionately affects vulnerable people with type 2 diabetes mellitus and interventions targeting this population are therefore relevant. A systematic review and meta-analysis was performed to assess the evidence for an effect of psychosocial interventions for reducing DD, and, secondly HbA1c, depression, and health-related quality of life in vulnerable people with type 2 diabetes mellitus. Vulnerability encompasses poor glycemic control (HbA1c >7.5%) and at least one additional risk factor for poor diabetes outcomes such as low educational level, comorbidity, and risky lifestyle behavior. The interventions should be theoretically founded and include cognition- or emotion-focused elements. We systematically searched four databases for articles published between January 1995 and March 2018. Eighteen studies testing a variety of psychosocial interventions in 4,066 patients were included. We adhered to the Cochrane methodology and PRISMA guidelines. Review Manager 5.3 was used for data extraction and risk of bias assessment, and Grades of Recommendation, Assessment, Development and Evaluation for assessing the quality of the evidence. Data were pooled using the fixed or random effects method as appropriate. We investigated effects of individual vs group, intensive vs brief interventions, and interventions with and without motivational interviewing in subgroup analyses. To assess the robustness of effect estimates, sensitivity analyses excluding studies with high risk of bias and attrition >20% were conducted. We found low to moderate quality evidence for a significant small effect of psychosocial interventions on DD, and very low to moderate quality evidence for no effect on HbA1c, both outcomes assessed at 3, 6, 12, and 24 months follow-up. The effect on depression was small, while there was no effect on health-related quality of life. Exploratory subgroup analyses suggested that interventions using motivational interviewing and individual interventions were associated with incremental effects on DD. Likewise, intensive interventions were associated with significant reductions in both DD and HbA1c. Keywords: diabetes distress, HbA1c, meta-analysis, psychosocial interventions, type 2 diabetes, vulnerable populations

Karen Christina Walker,1 Laura Staun Valentiner,1,2 Henning Langberg1 1CopenRehab, Section of Social Medicine, Department of Public Health, Faculty of Health, 2Center for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim: To explore motivational factors for initiating, implementing, and maintaining physical activity following a rehabilitation program for patients with type 2 diabetes mellitus.Methods: Semi-structured, individual, qualitative interviews with five informants from the InterWalk trial were conducted at three separate occasions; at initiation of the rehabilitation program, at completion of the 12-week program, and 52 weeks after enrolment. Interviews were audio-recorded, transcribed, and analyzed according to Systematic Text Condensation. The framework of Self-Determination Theory was applied to guide analysis after identification of preliminary themes.Results: Commitment and obligation were emphasized as being motivational in initiating physical activity. Toward the termination of the program, this was challenged by an expressed need for autonomy. Successful behavioral change was characterized by transfer of commitment to a new structure in everyday life, which also honored the request for autonomy. Feeling capable of participating in physical activity was facilitated through knowledge, practical experience, and progress and considered motivational, whereas lack of progress extinguished motivation. Finally, enjoyment of the activity was determining for long-term maintenance of physical activity behavior.Conclusion: Satisfaction of innate psychological needs leads to more autonomous regulation of behavior and, through this study, we investigated determining factors for extrinsically motivated behavior and factors of importance to the internalization process. Keywords: self-determination theory, type 2 diabetes mellitus, adherence, behavioral change, motivation

Katrine Rutkær Molin,1 Ingrid Egerod,2 Laura Staun Valentiner,1 Peter Lange,3 Henning Langberg1 1CopenRehab, Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; 2Department of Neuroanaesthesiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 3Section of Social Medicine, Department of Public Health, University of Copenhagen, Copenhagen, Denmark Background: In Denmark, the treatment of COPD is mainly managed by general practitioners (GPs). Pulmonary rehabilitation (PR) is available to patients with COPD in the local community by GP referral, but in practice, many patients do not participate in rehabilitation. The aim of our study was to explore 1) GPs’ perceptions of their role and responsibility in the rehabilitation of patients with COPD, and 2) GPs’ perceptions of how patients manage their COPD.Methods: The study was based on a qualitative design with semi-structured key-informant interviews with GPs. Investigator triangulation was applied during data generation, and analysis was done using thematic analysis methodology.Results: Our main findings were that GPs relied on patients themselves to take the initiative to make clinic appointments and on professionals at health centers to provide the PR including consultations on lifestyle changes. The GPs experienced that patients chose to come to the clinic when they were in distress and that patients either declined or had poor adherence to rehabilitation when offered. The GPs were relieved that the health centers had taken over the responsibility of rehabilitation as GPs lacked the resources to discuss rehabilitation and follow up on individual plans.Conclusion: Our study suggested a potential self-reinforcing problem with the treatment of COPD being mainly focused on medication rather than on PR. Neither GPs nor patients used a proactive approach. Further, GPs were not fully committed to discuss non-pharmacological treatment and perceived the patients as unmotivated for PR. As such, there is a need for opti­mizing non-pharmacological treatment of COPD and in particular the referral process to PR. Keywords: non-pharmacological treatment, motivation theory, primary care, treatment approach, pulmonary rehabilitation, qualitative research

Mathias Ried-Larsen,1–3 Reimar W Thomsen,2,4 Klara Berencsi,4 Cecilie F Brinkløv,1,5 Charlotte Brøns,1,5 Laura S Valentiner,1,6 Kristian Karstoft,1,3 Henning Langberg,1,6 Allan A Vaag,1,2,5 Bente K Pedersen,1,3 Jens S Nielsen7 1Department of Infectious Diseases, Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, 2The Danish Diabetes Academy, Odense University Hospital, Odense, 3Department of Infectious Diseases, Centre of Inflammation and Metabolism, Rigshospitalet, University of Copenhagen, Copenhagen, 4Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus Nord, 5Department of Endocrinology (Diabetes and Metabolism), Rigshospitalet, University of Copenhagen, 6CopenRehab, Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, 7Department of Endocrinology, Odense University Hospital, Odense, Denmark Abstract: Promoting physical activity is a first-line choice of treatment for patients with type 2 diabetes (T2D). However, there is a need for more effective tools and technologies to facilitate structured lifestyle interventions and to ensure a better compliance, sustainability, and health benefits of exercise training in patients with T2D. The InterWalk initiative and its innovative application (app) for smartphones described in this study were developed by the Danish Centre for Strategic Research in T2D aiming at implementing, testing, and validating interval walking in patients with T2D in Denmark. The interval walking training approach consists of repetitive 3-minute cycles of slow and fast walking with simultaneous intensity guiding, based on the exercise capacity of the user. The individual intensity during slow and fast walking is determined by a short initial self-conducted and audio-guided fitness test, which combined with automated audio instructions strives to motivate the individual to adjust the intensity to the predetermined individualized walking intensities. The InterWalk app data are collected prospectively from all users and will be linked to the unique Danish nationwide databases and administrative registries, allowing extensive epidemiological studies of exercise in patients with T2D, such as the level of adherence to InterWalk training and long-term effectiveness surveys of important health outcomes, including cardiovascular morbidity and mortality. Currently, the InterWalk app has been downloaded by >30,000 persons, and the achieved epidemiological data quality is encouraging. Of the 9,466 persons providing personal information, 80% of the men and 62% women were overweight or obese (body mass index ≥25). The InterWalk project represents a contemporary technology-driven public health approach to monitor real-life exercise adherence and to propagate improved health through exercise intervention in T2D and in the general population. Keywords: exercise, telemedicine, cell phones

We have developed a direct method for the measurement of human musculoskeletal collagen synthesis on the basis of the incorporation of stable isotope-labeled proline or leucine into protein and have used it to measure the rate of synthesis of collagen in tendon, ligament, muscle, and skin. In postabsorptive, healthy young men (28 [+ or -] 6 yr) synthetic rates for tendon, ligament, muscle, and skin collagen were 0.046 [+ or -] 0.005, 0.040 [+ or -] 0.006, 0.016 [+ or -] 0.002, and 0.037 [+ or -] 0.003%/h, respectively (means [+ or -] SD). In postabsorptive, healthy elderly men (70 [+ or -] 6 yr) the rate of skeletal muscle collagen synthesis is greater than in the young (0.023 [+ or -] 0.002%/h, P < 0.05 vs. young). The rates of synthesis of tendon and ligament collagen are similar to those of mixed skeletal muscle protein in the postabsorptive state, whereas the rate for muscle collagen synthesis is much lower in both young and elderly men. After nutritient provision, collagen synthesis was unaltered in tendon and skeletal muscle, remaining at postabsorptive values (young: tendon, 0.045 [+ or -] 0.008%/h; muscle, 0.016 [+ or -] 0.003%/h; elderly: muscle, 0.024 [+ or -] 0.003%/h). These results demonstrate that the rate of human musculoskeletal tissue collagen synthesis can be directly and robustly measured using stable isotope methodology. stable-isotope tracers; musculoskeletal collagen synthesis; nutrition; aging

The binding properties and dynamics of Humicola lanuginosa lipase (H11) and the inactive mutant S146A have been investigated using fluorescence spectroscopy and molecular dynamics simulations. They exhibit different binding behaviour for phosphatidycholine and phosphatidylglycerol liposomes. This is in agreement with molecular dynamics simulations and results show that hinges of the active site lid are more flexible in wild type H11 than in S146A.