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  • 1.
    Atabaki-Pasdar, Naeimeh
    et al.
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Ohlsson, Mattias
    Halmstad University, School of Information Technology, Halmstad Embedded and Intelligent Systems Research (EIS), CAISR - Center for Applied Intelligent Systems Research. Department of Astronomy and Theoretical Physics, Lund University, Lund, Sweden.
    Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts2020In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 17, no 6, article id e1003149Article in journal (Refereed)
    Abstract [en]

    Background Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. Methods and findings We utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (<5% or ≥5%) available for 1,514 participants. We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and random forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operating characteristic area under the curve (ROCAUC) of 0.84 (95% CI 0.82, 0.86; p < 0.001), which compared with a ROCAUC of 0.82 (95% CI 0.81, 0.83; p < 0.001) for a model including 9 clinically accessible variables. The IMI DIRECT prediction models outperformed existing noninvasive NAFLD prediction tools. One limitation is that these analyses were performed in adults of European ancestry residing in northern Europe, and it is unknown how well these findings will translate to people of other ancestries and exposed to environmental risk factors that differ from those of the present cohort. Another key limitation of this study is that the prediction was done on a binary outcome of liver fat quantity (<5% or ≥5%) rather than a continuous one. Conclusions In this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see: https://www.predictliverfat.org/) and made it available to the community. © This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

  • 2.
    Berg, Marie
    et al.
    Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Erlandsson, Lena-Karin
    Department of Health Sciences, Faculty of Medicine, Lund University, Lund, Sweden.
    Sparud-Lundin, Carina
    Institute of Health and Care Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Breastfeeding and its impact on daily life in women with type 1 diabetes during the first six months after childbirth: a prospective cohort study2012In: International Breastfeeding Journal, ISSN 1746-4358, E-ISSN 1746-4358, Vol. 7, article id 20Article in journal (Refereed)
    Abstract [en]

    Background: For mothers with diabetes, breastfeeding is a great challenge due to their struggle with potentially unstable blood glucose levels. This paper explores breastfeeding attitudes and impact of breastfeeding on the daily life of mothers with type 1 diabetes compared with non-diabetic mothers.Methods: We performed a prospective cohort study of 108 mothers with type 1 diabetes and a reference group of 104 mothers in the west of Sweden. Data were collected through medical records and structured telephone interviews at 2 and 6 months after childbirth.Results: Women in both the diabetes group and the reference group had high levels of confidence (84% and 93% respectively) in their breastfeeding capacity before childbirth, and 90% assessed breastfeeding as a positive and an important experience during the six months of follow-up. About 80% assessed breastfeeding as influencing daily life 'very much' or 'quite a lot' at 2 months as did 60% at 6 months, with no difference between the groups. In mothers with diabetes, the impact of breastfeeding on the priority of other duties decreased over time, as did feelings of time pressure and negative effects on patterns of sleep. Compared to the reference group, mothers with diabetes at 6 months remained more affected by disruptions in daily life and they felt more worried about their health both at 2 and 6 months after childbirth. For the reference group mothers' sensitivity to unexpected disruptions in daily routines decreased between 2 and 6 months after childbirth, and they expressed a greater need to organize their time than mothers with diabetes.Conclusion: Mothers with diabetes type 1 express more worry for own health and are more sensitive to distruptions. To balance their everyday life and to reduce the risk of stress and illhealth they are therefor, compared to other mothers, likely to need additional professional and peer support. © 2012 Berg et al.; licensee BioMed Central Ltd.

  • 3.
    Garthwaite, Taru
    et al.
    Turku University Hospital, Turku, Finland.
    Sjöros, Tanja
    Turku University Hospital, Turku, Finland.
    Koivumäki, Mikko
    Turku University Hospital, Turku, Finland.
    Laine, Saara
    Turku University Hospital, Turku, Finland.
    Vähä-Ypyä, Henri
    UKK Institute Finland, Tampere, Finland.
    Saarenhovi, Maria
    Turku University Hospital, Turku, Finland.
    Kallio, Petri
    Turku University Hospital, Turku, Finland; University of Turku, Turku, Finland.
    Löyttyniemi, Eliisa
    University of Turku, Turku, Finland.
    Sievänen, Harri
    UKK Institute Finland, Tampere, Finland.
    Houttu, Noora
    University of Turku, Turku, Finland.
    Laitinen, Kirsi
    University of Turku, Turku, Finland.
    Kalliokoski, Kari
    Turku University Hospital, Turku, Finland.
    Vasankari, Tommi
    UKK Institute Finland, Tampere, Finland; Tampere University, Tampere, Finland.
    Knuuti, Juhani
    Turku University Hospital, Turku, Finland.
    Heinonen, Ilkka
    Halmstad University, School of Business, Innovation and Sustainability, The Rydberg Laboratory for Applied Sciences (RLAS). Turku University Hospital, Turku, Finland.
    Standing is associated with insulin sensitivity in adults with metabolic syndrome2021In: Journal of Science and Medicine in Sport, ISSN 1440-2440, E-ISSN 1878-1861, Vol. 24, no 12, p. 1255-1260Article in journal (Refereed)
    Abstract [en]

    Objectives: To determine how components of accelerometer-measured sedentary behavior (SB) and physical activity (PA), and fitness are associated with insulin sensitivity in adults with metabolic syndrome. Design: Cross-sectional. Methods: Target population was middle-aged (40–65 years) sedentary adults with metabolic syndrome. SB, breaks in SB, standing, and PA were measured for four weeks with hip-worn accelerometers. VO2max (ml/min/kg) was measured with maximal cycle ergometry. Insulin sensitivity was determined by hyperinsulinaemic-euglycaemic clamp (M-value) and fasting blood sampling (HOMA-IR, insulin). Multivariable regression was used for analyses. Results: Sixty-four participants (37 women; 58.3 [SD 6.8] years) were included. Participants spent 10.0 (1.0) h sedentary, 1.8 (0.6) h standing, and 2.7 (0.6) h in PA and took 5149 (1825) steps and 29 (8) breaks daily. In sex-, age- and accelerometer wear time-adjusted model SB, standing, steps and VO2max were associated with M-value (β = −0.384; β = 0.400; β = 0.350; β = 0.609, respectively), HOMA-IR (β = 0.420; β = −0.548; β = −0.252; β = −0.449), and insulin (β = 0.433; β = −0.541; β = −0.252; β = −0.453); all p-values < 0.05. Breaks associated only with M-value (β = 0.277). When further adjusted for body fat %, only standing remained significantly associated with HOMA-IR (β = −0.381) and insulin (β = −0.366); significance was maintained even when further adjusted for SB, PA and fitness. Light and moderate-to-vigorous PA were not associated with insulin sensitivity. Conclusions: Standing is associated with insulin sensitivity markers. The association with HOMA-IR and insulin is independent of adiposity, PA, SB and fitness. Further studies are warranted, but these findings encourage replacing sitting with standing for potential improvements in insulin sensitivity in adults at increased type 2 diabetes risk. © 2021 The Authors.

  • 4.
    Garthwaite, Taru
    et al.
    Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Sjöros, Tanja
    Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Laine, Saara
    Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Koivumäki, Mikko
    Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Vähä-Ypyä, Henri
    UKK Institute for Health Promotion Research, Tampere, Finland.
    Eskola, Olli
    Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Rajander, Johan
    Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Kallio, Petri
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Saarenhovi, Maria
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Löyttyniemi, Eliisa
    University of Turku, Turku, Finland.
    Sievänen, Harri
    UKK Institute for Health Promotion Research, Tampere, Finland.
    Houttu, Noora
    University of Turku, Turku, Finland.
    Laitinen, Kirsi
    University of Turku, Turku, Finland.
    Kalliokoski, Kari
    Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Vasankari, Tommi
    UKK Institute for Health Promotion Research, Tampere, Finland; University of Tampere, Tampere, Finland.
    Knuuti, Juhani
    Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Heinonen, Ilkka
    Halmstad University, School of Business, Innovation and Sustainability. Turku PET Centre, Turku, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Turku, Finland; Turku University Hospital, Turku, Finland.
    Associations of sedentary time, physical activity, and fitness with muscle glucose uptake in adults with metabolic syndrome2022In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 33, no 3, p. 353-358Article in journal (Refereed)
    Abstract [en]

    Objective: The objective of the study was to investigate the associations of sedentary time, physical activity, and cardiorespiratory fitness with skeletal muscle glucose uptake (GU). Methods: Sedentary time and physical activity were measured with accelerometers and VO2max with cycle ergometry in 44 sedentary adults with metabolic syndrome. Thigh muscle GU was determined with [18F]FDG-PET imaging. Results: Sedentary time (β = −0.374), standing (β = 0.376), steps (β = 0.351), and VO2max (β = 0.598) were associated with muscle GU when adjusted for sex, age, and accelerometer wear time. Adjustment for body fat-% turned all associations non-significant. Conclusion: Body composition is a more important determinant of muscle GU in this population than sedentary time, physical activity, or fitness. © 2022 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.

  • 5.
    Hampe, Christiane
    et al.
    University of Washington, Seattle, US.
    Rowley, Merrill
    University of Washington, Seattle, US.
    Nandakumar, Kutty Selva
    University of Washington, Seattle, US; kutty-selva.nandakumar@hh.se.
    Pathogenic and Protective Autoantibodies in Arthritis and Diabetes2019In: Autoimmune Disorders: Risk Factors, Pathogenesis and Treatments / [ed] Kutty Selva Nandakumar, USA: Nova Science Publishers, Inc., 2019, 1, p. 133-169Chapter in book (Refereed)
    Abstract [en]

    Autoimmune diseases are characterized by the presence of serum autoantibodies of various specificities but the significance of these autoantibodies in the development of symptoms is unclear. Most studies have been carried out using polyclonal sera. However, antibodies’ effects depend on Fab-mediated diversity in epitope specificity, and also on Fc-mediated effects dependent on immunoglobulin class and subclass, immune complex-induced activation of complement, and the milieu in which the reaction occurs. Monoclonal autoantibodies have rarely been studied, but increasingly such mAb are becoming available. These include human mAb to GAD65 from patients with newly diagnosed type 1 diabetes, and mouse mAb to type II collagen that have the capacity to induce collagen antibody induced arthritis (CAIA). In both systems, there is clear evidence that the epitope specificity of the antibodies is related to the expression of the disease, and protective antibodies may occur. © 2004 - 2023 Nova Science Publishers

  • 6.
    Jendle, J.
    et al.
    Örebro University, Örebro, Sweden.
    Agvall, B.
    Region Halland, Research and Development, Halmstad, Sweden.
    Galozy, Alexander
    Halmstad University, School of Information Technology.
    Adolfsson, P.
    Hospital of Halland, Kungsbacka, Sweden.
    Better Glycemic Control and Higher Use of Advanced Diabetes Technology in Age Group 0-17 Yrs Compared to 18-25 Yrs with Type 1 Diabetes2022In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 24, no S1, p. A127-A127Article in journal (Refereed)
  • 7.
    Johnson, Petra
    et al.
    Halmstad University, School of Social and Health Sciences (HOS).
    Lindh, Thanyawan
    Halmstad University, School of Social and Health Sciences (HOS).
    Diabetes mellitus typ 2 patientens behov av stöd2011Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    There are 365 000 people in Sweden who suffer from diabetes mellitus type 2. The disease is caused by factors that are genetic or environmental. The disease occurs from insulin resistance in the cells of the muscle, liver or fat tissue. The disease can result in serious complications. The patient has a need for support from the healthcare professionals to be able to manage self-management and the life- style changes that are necessary. The patient can through empowerment take charge over the disease. The aim of this study was to define how patients who suffer from diabetes mellitus type 2 describe their need for support. The literature study consists of ten scientific articles, six qualitative, two quantitative and two articles that were both qualitative and quantitative. The result is presented as five themes: the patient’s need for information as support, the patient’s need for knowledge as support, the patient’s need for education as support, the patient’s need for social support, the patient’s need for support from healthcare professionals. The patients desired information from the healthcare professionals about self- monitoring of blood glucose, medications, diets and exercise to be able to perform self-management. Peer education was appreciated by patients, particularly with patients with the same disease and experience as their own. The support from the surroundings could strengthen patient’s quality of life. If the need for support from the healthcare professionals was experienced as adequate the disease seemed more manageable by the patients. Therefore it is relevant, already in the beginning of the nursing program, to emphasize the need for support with diabetes mellitus type 2. Registered nurses can then include the knowledge within the clinic. Further research within healthcare is recommended, especially studies within Sweden that investigate the patient’s need for support.

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  • 8.
    Koro, Catalin
    Halmstad University, School of Business and Engineering (SET), Biological and Environmental Systems (BLESS).
    Mätningar av kortisolkoncentrationen i saliv under två perioder där stressfaktorn upplevs variera.: Analys av kortisolkoncentrationen och intraindividuell stabilitet inom cortisol awakening response (CAR).2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Version:1.0 StartHTML:0000000178 EndHTML:0000005278 StartFragment:0000002640 EndFragment:0000005242 SourceURL:file://localhost/Volumes/NAMNLOS/Examensarbete%20kortisol.doc

    Föreliggande studie syftar till att försöka utläsa skillnader mellan två olika perioder då den personliga stressfaktorn upplevs vara olika intensiv. Undersökningen syftar även till att studera huruvida den mänskliga kortisolutsöndringens diurnala upp - och ned gångar följer en intraindividuell stabilitet av CAR (cortisol awakening responce). Detta skulle innebära ett upprepande mönster av kortisolkoncentrationens magnitud och mätvärde inom varje individ från dag till dag, vid uppvaknandet och 30 minuter efter.

    Undersökningen har genomförts som en pilotstudie där en försökspersons kortisolkoncentration i saliv har mätts genom enzymkopplad immunabsorberande analys (ELISA). För att jämföra mätserierna inom de olika perioderna med varandra har även en variationsanalys av typen Analysis of variance (ANOVA) utförts med hjälp av programvaran SPSS. Då provernas mätvärde har analyserats och jämförts med varandra har ett resultat kunnat fastställas.

    Eftersom utsöndringen av den individuella kortisolkoncentrationen lätt påverkas av omgivningsfaktorer användes endast en försöksperson, författaren, vilket underlättade en detaljerad analys där observation av påverkande faktorer lätt kunde tas med i beräkningen för att fastställa ett tillförlitligt resultat. Försökspersonen, kvinna 21 år, utförde 6 provtagningar under två perioder som upplevdes ha olika hög stressfaktor. Perioderna innehöll två arbetsdagar. Parallellt med provtagningen fördes noggranna dagboksanteckningar för att underlätta analyseringsarbetet.

    Resultatet uppvisar en intraindividuell stabilitet av CAR hos försökspersonen. Studien visar även en skillnad mellan de två perioderna genom en högre procentuell ökning av CAR under den period då stressfaktorn upplevdes som mer intensiv.

    Den tydliga skillnaden av kortisolkoncentrationens mätvärde mellan de olika dagarna indikerar även att livsstil, fysisk aktivitet och drömmar kan påverka utseendet av kortisolkoncentrationskurvans diurnala upp – och nedgångar.

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  • 9.
    Linderoth, Anna
    et al.
    Halmstad University, School of Social and Health Sciences (HOS).
    John, Cajsa
    Halmstad University, School of Social and Health Sciences (HOS).
    Rouhi, Anna- Liza
    Halmstad University, School of Social and Health Sciences (HOS).
    Abrupt och otryggt: - ungdomar med diabetes i övergången från prediatrik till vuxenvård2010Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Problem: Övergången från pediatrik till vuxenvård tillfredsställer inte de behov som ungdomar med diabetes har vilket leder till att de känner sig osynliga i vården och osäkra i sin egenvård.

    Syfte: Syftet var att belysa hur ungdomar med diabetes typ 1 upplever och hanterar sjukdomen i övergången från pediatrik till vuxenvård och processens påverkande faktorer.

    Metod: Med hjälp av 14 vetenskapliga artiklar och en avhandling formades litteraturstudien.

    Resultat och konklusion: Att utforska sin identitet och att tänja på gränser är ett naturligt beteende under adolescensen. Detta beteende i kombination med diabetessjukdomen leder till en ökad risk för diabetesrelaterade komplikationer. Övergången mellan pediatrik och vuxenvård upplevdes av ungdomarna som problematisk. Faktorer som försvårade övergången från pediatrik till vuxenvård var klyftan i vårdkultur mellan vårdenheterna. Vuxenvården innebar ett större ansvarstagande från individen, mindre vårdtillgänglighet och mindre delaktighet från föräldrar samt bristande kontinuitet och uppföljning. Skillnaderna i vårdkulturen mellan pediatrik och vuxenvård bör minskas, och riktlinjerna kring övergången bör tydligare klargöras.  

    Implikation: Framtida forskning bör fokusera på de faktorer som, enligt ungdomar med diabetes anser underlätta övergången mellan pediatrik och vuxenvård. Forskningen bör även inriktas på sjuksköterskans förståelse för den problematik som ungdomar med diabetes typ 1 har i adolescensen.

     

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  • 10.
    Lindholm, Annelie
    et al.
    Halmstad University, School of Health and Welfare. Research and Development Center Spenshult, Halmstad, Sweden.
    Almqvist-Tangen, Gerd
    Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Child Health Care Unit, Region Halland, Halmstad, Sweden.
    Alm, Bernt
    Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bremander, Ann
    Research and Development Center Spenshult, Halmstad, Sweden; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
    Dahlgren, Jovanna
    Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Roswall, Josefine
    Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Pediatrics, Halland Hospital, Halmstad, Sweden.
    Staland-Nyman, Carin
    Halmstad University, School of Health and Welfare.
    Bergman, Stefan
    Research and Development Center Spenshult, Halmstad, Sweden; Primary Health Care Unit, Department of Public Health and Community Medicine, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Early rapid weight gain, parental body mass index and the association with an increased waist-to-height ratio at 5 years of age2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 9, article id e0273442Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: Obesity-related adverse health consequences are closely associated with abdominal obesity. Risk factors for overweight and obesity have been studied but there is a lack of information regarding risk factors for abdominal obesity, especially in the preschool population. The aim of the present study was to examine early life risk factors for an increased waist-to-height ratio (WHtR) in children at five years of age and, in addition, to investigate if these risk factors also were associated with overweight or obesity. 

    Subjects/Methods: The study population comprised 1,540 children from a population-based longitudinal birth cohort study that included 2,666 Swedish children. The children were included if they had complete growth data for the analyses used in this study. Children were classified as having WHtR standard deviation scores (SDS) ≥ 1 or < 1 at five years of age, according to Swedish reference values, and as having body mass index standard deviation scores (BMISDS) for overweight/obesity, or normal weight/underweight according to the International Obesity Task Force criteria. Associations between child-related, socioeconomic status-related, parental health-related and nutrition- and feeding practice-related factors during the first two years and a WHtRSDS ≥ 1 or a BMISDS for overweight/obesity at five years were investigated with logistic regression analyses. 

    Results: At five years of age, 15% of the children had WHtRSDS ≥ 1 and 11% had overweight or obesity. In multivariable analyses, rapid weight gain (RWG) during 0-6 months (OR: 1.90, 95% CI: 1.23–2.95, p=0.004), maternal pre-pregnancy BMI (1.06, 1.01–1.11, p=0.019) and paternal BMI (1.11, 1.01–1.21, p=0.028) were associated with WHtRSDS ≥ 1. RWG during 0-6 months (2.53, 1.53–4.20, p<0.001), 6-12 months (2.82, 1.37–5.79, p=0.005), and maternal pre-pregnancy BMI (1.11, 1.06–1.17, p<0.001) were associated with overweight or obesity.

    Conclusions: Early risk factors, including rapid weight gain, are associated with increased WHtRSDS and overweight or obesity at 5 years of age. Preventive interventions should target early RWG and parental overweight and obesity. 

     

  • 11.
    Liu, Shengxin
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Ludvigsson, Jonas F.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, United Kingdom; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
    Svensson, Ann-Marie
    Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gudbjörnsdottir, Soffia
    Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden; Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Tideman, Magnus
    Halmstad University, School of Health and Welfare, Centre of Research on Welfare, Health and Sport (CVHI), The Wigforss Group.
    Serlachius, Eva
    Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Service, Region Stockholm, Stockholm, Sweden.
    Butwicka, Agnieszka
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden; Child and Adolescent Psychiatry, Stockholm Health Care Service, Region Stockholm, Stockholm, Sweden; Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland.
    Neurodevelopmental Disorders, Glycemic Control, and Diabetic Complications in Type 1 Diabetes: a Nationwide Cohort Study2021In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 106, no 11, p. e4459-e4470Article in journal (Refereed)
    Abstract [en]

    Context: Neurodevelopmental disorders are more prevalent in childhood-onset type 1 diabetes than in the general population, and the symptoms may limit the individual’s ability for diabetes management.

    Objective: This study investigated whether comorbid neurodevelopmental disorders are associated with long-term glycemic control and risk of diabetic complications.

    Methods: This population-based cohort study used longitudinally collected data from Swedish registers. We identified 11 326 individuals born during 1973-2013, diagnosed with type 1 diabetes during 1990-2013 (median onset age: 9.6 years). Among them, 764 had a comorbid neurodevelopmental disorder, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, and intellectual disability. We used multinomial logistic regression to calculate odds ratios (ORs) of having poor glycemic control (assessed by glycated hemoglobin [HbA1c]) and Cox regression to estimate hazard ratios (HRs) of nephropathy and retinopathy.

    Results: The median follow-up was 7.5 years (interquartile range [IQR] 3.9, 11.2). Having any neurodevelopmental disorder (ORadjusted 1.51 [95% CI 1.13, 2.03]), or ADHD (ORadjusted 2.31 [95% CI 1.54, 3.45]) was associated with poor glycemic control (mean HbA1c > 8.5%). Increased risk of diabetic complications was observed in patients with comorbid neurodevelopmental disorders (HRadjusted 1.72 [95% CI 1.21, 2.44] for nephropathy, HRadjusted 1.18 [95% CI 1.00, 1.40] for retinopathy) and patients with ADHD (HRadjusted 1.90 [95% CI 1.20, 3.00] for nephropathy, HRadjusted 1.33 [95% CI 1.07, 1.66] for retinopathy). Patients with intellectual disability have a particularly higher risk of nephropathy (HRadjusted 2.64 [95% CI 1.30, 5.37]).

    Conclusion: Comorbid neurodevelopmental disorders, primarily ADHD and intellectual disability, were associated with poor glycemic control and a higher risk of diabetic complications in childhood-onset type 1 diabetes. © The Author(s) 2021.

  • 12.
    Norha, Jooa
    et al.
    University of Turku, Turku, Finland.
    Sjöros, Tanja
    University of Turku, Turku, Finland.
    Garthwaite, Taru
    University of Turku, Turku, Finland.
    Laine, Saara
    University of Turku, Turku, Finland.
    Saarenhovi, Maria
    University of Turku, Turku, Finland.
    Kallio, Petri
    University of Turku, Turku, Finland.
    Laitinen, Kirsi
    University of Turku, Turku, Finland.
    Houttu, Noora
    University of Turku, Turku, Finland.
    Vähä-Ypyä, Henri
    Ukk Institute For Health Promotion Research, Tampere, Finland.
    Sievänen, Harri
    Ukk Institute For Health Promotion Research, Tampere, Finland.
    Löyttyniemi, Eliisa
    University of Turku, Turku, Finland.
    Vasankari, Tommi
    Ukk Institute For Health Promotion Research, Tampere, Finland; University Of Tampere, Tampere, Finland.
    Knuuti, Juhani
    University of Turku, Turku, Finland.
    Kalliokoski, Kari K.
    University of Turku, Turku, Finland.
    Heinonen, Ilkka
    Halmstad University, School of Business, Innovation and Sustainability. University Of Turku, Turku, Finland.
    Effects of reducing sedentary behavior on cardiorespiratory fitness in adults with metabolic syndrome: A 6-month RCT2023In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 33, no 8, p. 1452-1461Article in journal (Refereed)
    Abstract [en]

    Introduction:

    Poor cardiorespiratory fitness (CRF) is associated with adverse health outcomes. Previous observational and cross-sectional studies have suggested that reducing sedentary behavior (SB) might improve CRF. Therefore, we investigated the effects of a 6-month intervention of reducing SB on CRF in 64 sedentary inactive adults with metabolic syndrome in a non-blind randomized controlled trial.

    Materials and Methods:

    In the intervention group (INT, n = 33), the aim was to reduce SB by 1 h/day for 6 months without increasing exercise training. Control group (CON, n = 31) was instructed to maintain their habitual SB and physical activity. Maximal oxygen uptake (VO2max) was measured by maximal graded bicycle ergometer test with respiratory gas measurements. Physical activity and SB were measured during the whole intervention using accelerometers.

    Results:

    Reduction in SB did not improve VO2max statistically significantly (group × time p &gt; 0.05). Maximal absolute power output (Wmax) did not improve significantly but increased in INT compared to CON when scaled to fat free mass (FFM) (at 6 months INT 1.54 [95% CI: 1.41, 1.67] vs. CON 1.45 [1.32, 1.59] Wmax/kgFFM, p = 0.036). Finally, the changes in daily step count correlated positively with the changes in VO2max scaled to body mass and FFM (r = 0.31 and 0.30, respectively, p &lt; 0.05).

    Discussion:

    Reducing SB without adding exercise training does not seem to improve VO2max in adults with metabolic syndrome. However, succeeding in increasing daily step count may increase VO2max. © 2023 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.

  • 13.
    Rebelos, Eleni
    et al.
    University of Turku, Turku, Finland.
    Bucci, Marco
    University of Turku, Turku, Finland.
    Karjalainen, Tomi
    University of Turku, Turku, Finland.
    Oikonen, Vesa
    University of Turku, Turku, Finland.
    Bertoldo, Alessandra
    University of Padova, Padua, Italy.
    Hannukainen, Jarna C.
    University of Turku, Turku, Finland.
    Virtanen, Kirsi A.
    University of Turku, Turku, Finland; University of Eastern Finland, Kuopio, Finland.
    Latva-Rasku, Aino
    University of Turku, Turku, Finland.
    Hirvonen, Jussi
    Turku University Hospital, Turku, Finland; University of Turku, Turku, Finland.
    Heinonen, Ilkka
    Halmstad University, School of Business, Innovation and Sustainability, The Rydberg Laboratory for Applied Sciences (RLAS). University of Turku, Turku, Finland.
    Parkkola, Riitta
    Turku University Hospital, Turku, Finland; University of Turku, Turku, Finland.
    Laakso, Markku
    University of Eastern Finland, Kuopio, Finland.
    Ferrannini, Ele
    CNR, Pisa, Italy.
    Iozzo, Patricia
    University of Turku, Turku, Finland; CNR, Pisa, Italy.
    Nummenmaa, Lauri
    University of Turku, Turku, Finland.
    Nuutila, Pirjo
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Insulin resistance is associated with enhanced brain glucose uptake during euglycemic hyperinsulinemia: A large-scale PET cohort2021In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 44, no 3, p. 788-794Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of study participants across a wide range of age and insulin sensitivity. RESEARCH DESIGN AND METHODS [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 participants scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex,Mvalue from the clamp, steady-state insulin and free fatty acid levels, C-reactive protein levels, HbA1c, and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling. RESULTS Insulin sensitivity, indexed by theMvalue, was associated negatively with BGU in all brain regions, confirming that in insulin-resistant participants BGU was enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with additional increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein and free fatty acid levels, sex, and HbA1c were not associated with BGU. CONCLUSIONS In this large cohort of participants of either sex across a wide range of age and insulin sensitivity, insulin sensitivity was the best predictor of BGU. © 2021 by the American Diabetes Association.

  • 14.
    Rönneblad, Isa
    et al.
    Halmstad University, School of Business, Innovation and Sustainability.
    Ohrås, Elsa
    Halmstad University, School of Business, Innovation and Sustainability.
    Oral contraceptive phases and performance: Strength, anaerobic capacity, and lactate responce2023Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: Oral contraceptives are common among female athletes. Still, its effects on athletic performance are poorly investigated. Research in the area has increased in recent years. However, the study qualities and designs are often insufficient and with small sample sizes. Women are currently underrepresented in sport research, and to recruit more women in future studies and to facilitate female athletes’ choices about contraceptives, the impact of oral contraceptives on performance must be better understood.

    Aim: The aim was to investigate whether monophasic, combined oral contraceptive phases affected maximal muscle strength, anaerobic performance and the corresponding blood lactate response, or perceived mental and physical energy level among young women.

    Method: The study used a cross-over design where six participants were tested on two occasions. The participants were healthy women between 18 and 29 years old who had beenusing monophasic combined oral contraceptives for at least three months prior to the study. No criteria for training level was set. The Isometric mid-thigh pull (N) was used as an indicator ofmaximal muscle strength; and the Wingate anaerobic test (W) measured anaerobic performance and power with corresponding blood lactate levels (mmol/L) measured at 0, 3 and 5 minutes after termination of the test. The participants rated their current physical and mental energy level on both test occasions using a visual analog scale (0-10). Statistical analyses were madeusing Wilcoxon signed-ranked test.

    Results: Nine participants were recruited, of which six performed tests on both occasions. The participants had a mean (SD) age of 22.3 (1.8) years, a BMI of 23.3 (2.6) and all reached WHO’sphysical activity recommendations. No statistically significant differences in muscle strengthor anaerobic performance were found regarding peak force (p=0.60), peak power (p=0.35) oraverage power (p=0.60) between oral contraceptive phases. Neither were there any differencesin the blood lactate response to the Wingate test directly after (p=0.92), 3 minutes after (p=0.17) or 5 minutes after (p=0.60) the test. No differences in perceived mental energy level (p=0.35)or perceived physical energy level (p=0.17) between oral contraceptive phases were evident.

    Conclusion: Oral contraceptive phases did not affect maximal muscle strength, anaerobicperformance, blood lactate response or perceived mental or physical energy levels. Accordingly, there is no need to adapt training to oral contraceptive phases and women can berecruited in future research without consideration of oral contraceptive phases.

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  • 15.
    Shengxin, Liu
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Kuja-Halkola, Ralf
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Larsson, Henrik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden & School of Medical Sciences, Örebro University, Örebro, Sweden.
    Lichtenstein, Paul
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.
    Ludvigsson, Jonas
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden & Department of Pediatrics, Örebro University Hospital, Örebro, Sweden & Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK & Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA.
    Svensson, Ann-Marie
    Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden & Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gudbjörnsdottir, Soffia
    Swedish National Diabetes Register, Centre of Registers, Gothenburg, Sweden & Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Tideman, Magnus
    Halmstad University, School of Health and Welfare, Centre of Research on Welfare, Health and Sport (CVHI), The Wigforss Group.
    Serlachius, Eva
    Child and Adolescent Psychiatry, Stockholm Health Care Service, Region Stockholm, Sweden.
    Butwicka, Agnieszka
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden & Child and Adolescent Psychiatry, Stockholm Health Care Service, Region Stockholm, Sweden & Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland.
    Poor glycaemic control is associated with increased risk of neurodevelopmental disorders in childhood-onset type 1 diabetes: a population-based cohort study2021In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 64, no 4, p. 767-777Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: The aim of this study was to investigate the effect of childhood-onset type 1 diabetes on the risk of subsequent neurodevelopmental disorders, and the role of glycaemic control in this association. We hypothesised that individuals with poor glycaemic control may be at a higher risk of neurodevelopmental disorders compared with the general population, as well as compared with individuals with type 1 diabetes with adequate glycaemic control.

    Methods: This Swedish population-based cohort study was conducted using data from health registers from 1973 to 2013. We identified 8430 patients with childhood-onset type 1 diabetes (diagnosed before age 18 years) with a median age of diabetes onset of 9.6 (IQR 5.9–12.9) and 84,300 reference individuals from the general population, matched for sex, birth year and birth county. Cox models were used to estimate the effect of HbA1c on the risk of subsequent neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD) and intellectual disability.

    Results: During a median follow-up period of 5.6 years, 398 (4.7%) individuals with type 1 diabetes received a diagnosis of any neurodevelopmental disorder compared with 3066 (3.6%) in the general population, corresponding to an adjusted HR (HRadjusted) of 1.31 (95% CI 1.18, 1.46) after additionally adjusting for other psychiatric morbidity prior to inclusion, parental psychiatric morbidity and parental highest education level. The risk of any neurodevelopmental disorder increased with HbA1c levels and the highest risk was observed in patients with mean HbA1c >8.6% (>70 mmol/mol) (HRadjusted 1.90 [95% CI 1.51, 2.37]) compared with reference individuals without type 1 diabetes. In addition, when compared with patients with diabetes with HbA1c <7.5% (<58 mmol/mol), patients with HbA1c >8.6% (>70 mmol/mol) had the highest risk of any neurodevelopmental disorder (HRadjusted 3.71 [95% CI 2.75, 5.02]) and of specific neurodevelopmental disorders including ADHD (HRadjusted 4.16 [95% CI 2.92, 5.94]), ASD (HRadjusted 2.84 [95% CI 1.52, 5.28]) and intellectual disability (HRadjusted 3.93 [95% CI 1.38, 11.22]).

    Conclusions/interpretation: Childhood-onset type 1 diabetes is associated with an increased risk of neurodevelopmental disorders, with the highest risk seen in individuals with poor glycaemic control. Routine neurodevelopmental follow-up visits should be considered in type 1 diabetes, especially in patients with poor glycaemic control. © The Author(s) 2021

  • 16.
    Sjöros, Tanja
    et al.
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Laine, Saara
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Garthwaite, Taru
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Vaha-Ypya, Henri
    The UKK Institute for Health Promotion Research, Tampere, Finland.
    Loyttyniemi, Eliisa
    University of Turku, Turku, Finland.
    Koivumaki, Mikko
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Houttu, Noora
    University of Turku, Turku, Finland.
    Laitinen, Kirsi
    University of Turku, Turku, Finland.
    Kalliokoski, Kari K. K.
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Sievanen, Harri
    The UKK Institute for Health Promotion Research, Tampere, Finland.
    Vasankari, Tommi
    The UKK Institute for Health Promotion Research, Tampere, Finland; Tampere University, Tampere, Finland.
    Knuuti, Juhani
    University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Heinonen, Ilkka
    Halmstad University, School of Business, Innovation and Sustainability. University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Reducing Sedentary Time and Whole-Body Insulin Sensitivity in Metabolic Syndrome: A 6-Month Randomized Controlled Trial2023In: Medicine & Science in Sports & Exercise, ISSN 0195-9131, E-ISSN 1530-0315, Vol. 55, no 3, p. 342-353Article in journal (Refereed)
    Abstract [en]

    Purpose: This study aimed to investigate whether a reduction in daily sedentary behavior (SB) improves insulin sensitivity in adults with metabolic syndrome in 6 months, without adding intentional exercise training.

    Methods: Sixty-four sedentary inactive middle-age adults with overweight and metabolic syndrome (mean (SD) age, 58 (7) yr; mean (SD) body mass index, 31.6 (4.3) kg.m(-2); 27 men) were randomized into intervention and control groups. The 6-month individualized behavioral intervention supported by an interactive accelerometer and a mobile application aimed at reducing daily SB by 1 h compared with baseline. Insulin sensitivity by hyperinsulinemic euglycemic clamp, body composition by air displacement plethysmography, and fasting blood samples were analyzed before and after the intervention. SB and physical activity were measured with hip-worn accelerometers throughout the intervention.

    Results: SB decreased by 40 (95% confidence interval, 17-65) min.d(-1), and moderate-to-vigorous physical activity increased by 20 (95% confidence interval, 11-28) min.d(-1) on average in the intervention group with no significant changes in these outcomes in the control group. After 6 months, fasting plasma insulin decreased (similar to 1 mU.L-1) in the intervention group compared with the control group (time-group, P = 0.0081), but insulin sensitivity did not change in either group. The changes in body mass or adiposity did not differ between groups. Among all participants, the changes in SB and body mass correlated inversely with the change in insulin sensitivity (r = -0.31, -0.44; P = 0.025, 0.0005, respectively).

    Conclusions: An intervention aimed at reducing daily SB resulted in slightly decreased fasting insulin, but had no effects on insulin sensitivity or body adiposity. However, as the change in insulin sensitivity associated with the changes in SB and body mass, multifaceted interventions targeting to weight loss are likely to be beneficial in improving whole-body insulin sensitivity. © Lippincott Williams & Wilkins.

  • 17.
    Sjöros, Tanja
    et al.
    Turku PET Centre, Åbo, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Åbo, Finland; Turku University Hospital, Turku, Finland.
    Laine, Saara
    Turku PET Centre, Åbo, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Åbo, Finland; Turku University Hospital, Turku, Finland.
    Garthwaite, Taru
    Turku PET Centre, Åbo, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Åbo, Finland; Turku University Hospital, Turku, Finland.
    Vähä-Ypyä, Henri
    The UKK Institute for Health Promotion Research, Tampere, Finland.
    Koivumäki, Mikko
    Turku PET Centre, Åbo, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Åbo, Finland; Turku University Hospital, Turku, Finland.
    Eskola, Olli
    Turku PET Centre, Åbo, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Åbo, Finland; Turku University Hospital, Turku, Finland.
    Löyttyniemi, Eliisa
    Department of Biostatistics, University of Turku, Turku, Finland.
    Houttu, Noora
    Institute of Biomedicine, University of Turku, Turku, Finland.
    Laitinen, Kirsi
    Institute of Biomedicine, University of Turku, Turku, Finland.
    Kalliokoski, Kari K.
    Turku PET Centre, Åbo, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Åbo, Finland; Turku University Hospital, Turku, Finland.
    Sievänen, Harri
    The UKK Institute for Health Promotion Research, Tampere, Finland.
    Vasankari, Tommi
    The UKK Institute for Health Promotion Research, Tampere, Finland; Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
    Knuuti, Juhani
    Turku PET Centre, Åbo, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Åbo, Finland; Turku University Hospital, Turku, Finland.
    Heinonen, Ilkka H. A.
    Halmstad University, School of Business, Innovation and Sustainability. Turku PET Centre, Åbo, Finland; University of Turku, Turku, Finland; Åbo Akademi University, Åbo, Finland; Turku University Hospital, Turku, Finland.
    The effects of a 6-month intervention aimed to reduce sedentary time on skeletal muscle insulin sensitivity: a randomized controlled trial2023In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 325, no 2, p. E152-E162Article in journal (Refereed)
    Abstract [en]

    Sedentary behavior (SB) and physical inactivity associate with impaired insulin sensitivity. We investigated whether an intervention aimed at a 1-h reduction in daily SB during 6 mo would improve insulin sensitivity in the weight-bearing thigh muscles. Forty-four sedentary inactive adults [mean age 58 (SD 7) yr; 43% men] with metabolic syndrome were randomized into intervention and control groups. The individualized behavioral intervention was supported by an interactive accelerometer and a mobile application. SB, measured with hip-worn accelerometers in 6-s intervals throughout the 6-mo intervention, decreased by 51 (95% CI 22-80) min/day and physical activity (PA) increased by 37 (95% CI 18-55) min/day in the intervention group with nonsignificant changes in these outcomes in the control group. Insulin sensitivity in the whole body and in the quadriceps femoris and hamstring muscles, measured with hyperinsulinemic-euglycemic clamp combined with [18F]fluoro-deoxy-glucose PET, did not significantly change during the intervention in either group. However, the changes in hamstring and whole body insulin sensitivity correlated inversely with the change in SB and positively with the changes in moderate-to-vigorous PA and daily steps. In conclusion, these results suggest that the more the participants were able to reduce their SB, the more their individual insulin sensitivity increased in the whole body and in the hamstring muscles but not in quadriceps femoris. However, according to our primary randomized controlled trial results, this kind of behavioral interventions targeted to reduce sedentariness may not be effective in increasing skeletal muscle and whole body insulin sensitivity in people with metabolic syndrome at the population level.

    NEW & NOTEWORTHY Aiming to reduce daily SB by 1 h/day had no impact on skeletal muscle insulin sensitivity in the weight-bearing thigh muscles. However, successfully reducing SB may increase insulin sensitivity in the postural hamstring muscles. This emphasizes the importance of both reducing SB and increasing moderate-to-vigorous physical activity to improve insulin sensitivity in functionally different muscles of the body and thus induce a more comprehensive change in insulin sensitivity in the whole body.

  • 18.
    Taneera, Jalal
    et al.
    Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
    Rosengren, Anders
    Department of Physiological Sciences, Lund University, Lund, Sweden.
    Renstrom, Erik
    Department of Physiological Sciences, Lund University, Lund, Sweden.
    Nygren, Jens Martin
    Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University, Lund, Sweden.
    Serup, Palle
    Department of Developmental Biology, Hagedorn Research Institute, Copenhagen, Denmark.
    Rorsman, Patrik
    Department of Physiological Sciences, Lund University, Lund, Sweden.
    Jacobsen, Sten Eirik W
    Hematopoietic Stem Cell Laboratory, Lund University, BMC, B10, SE-221 84 Lund, Sweden.
    Failure of Transplanted Bone Marrow Cells to Adopt a Pancreatic β-Cell Fate2006In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 55, no 2, p. 290-296Article in journal (Refereed)
    Abstract [en]

    Recent studies in normal mice have suggested that transplanted bone marrow cells can transdifferentiate into pancreatic beta-cells at relatively high efficiency. Herein, adopting the same and alternative approaches to deliver and fate map-transplanted bone marrow cells in the pancreas of normal as well as diabetic mice, we further investigated the potential of bone marrow transplantation as an alternative approach for beta-cell replacement. In contrast to previous studies, transplanted bone marrow cells expressing green fluorescence protein (GFP) under the control of the mouse insulin promoter failed to express GFP in the pancreas of normal as well as diabetic mice. Although bone marrow cells expressing GFP under the ubiquitously expressed beta-actin promoter efficiently engrafted the pancreas of normal and hyperglycemic mice, virtually all expressed CD45 and Mac-1/Gr-1, demonstrating that they adopt a hematopoietic rather than beta-cell fate, a finding further substantiated by the complete absence of GFP(+) cells expressing insulin and the beta-cell transcription factors pancreatic duodenal homeobox factor-1 and homeodomain protein. Thus, transplanted bone marrow cells demonstrated little, if any, capacity to adopt a beta-cell fate.

  • 19.
    Uurasmaa, Tytti-Maria
    et al.
    University of Turku, Turku, Finland.
    Streng, Tomi
    University of Turku, Turku, Finland.
    Alkio, Milla
    University of Turku, Turku, Finland; Poznan University of Medical Sciences, Poznan, Poland.
    Heinonen, Ilkka
    Halmstad University, School of Business, Innovation and Sustainability, The Rydberg Laboratory for Applied Sciences (RLAS). Turku University Hospital, Turku, Finland.
    Anttila, Katja
    University of Turku, Turku, Finland.
    Short-term exercise affects cardiac function ex vivo partially via changes in calcium channel levels, without influencing hypoxia sensitivity2021In: Journal of physiology and biochemistry, ISSN 1138-7548, E-ISSN 1877-8755, Vol. 77, no 4, p. 639-651Article in journal (Refereed)
    Abstract [en]

    Exercise is known to improve cardiac recovery following coronary occlusion. However, whether short-term exercise can improve cardiac function and hypoxia tolerance ex vivo independent of reperfusion injury and the possible role of calcium channels in improved hypoxia tolerance remains unknown. Therefore, in the current study, heart function was measured ex vivo using the Langendorff method at different oxygen levels after a 4-week voluntary wheel-running regimen in trained and untrained male mice (C57Bl/6NCrl). The levels of cardiac Ca2+-channels: L-type Ca2+-channel (CACNA1C), ryanodine receptor (RyR-2), sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2), and sodium-calcium exchanger were measured using western blot. Trained mice displayed lower cardiac afterload pressure generation capacity (rate and amplitude), but unaltered hypoxia tolerance when compared to untrained mice with similar heart rates. The level of CACNA1C positively correlated with the pressure generation rate and amplitude. Furthermore, the CACNA1C-RYR-2 ratio also positively correlated with the pressure generation rate. While the 4-week training period was not enough to alter the intrinsic cardiac hypoxia tolerance, interestingly it decreased pressure generation capacity and slowed pressure decreasing capacity in the mouse hearts ex vivo. This reduction in pressure generation rate could be linked to the level of channel proteins in sarcolemmal Ca2+-cycling in trained mice. However, the Ca2+-channel levels did not differ significantly between the groups, and thus, the level of calcium channels cannot fully explain all the functional alterations, despite the detected correlations. Therefore, additional studies are warranted to reveal further mechanisms that contribute to the reduced intrinsic capacity for pressure production in trained mouse hearts. © 2021, The Author(s).

  • 20.
    Uurasmaa, Tytti-Maria
    et al.
    Laboratory of Animal Physiology, University of Turku, Turku, Finland.
    Streng, Tomi
    Laboratory of Animal Physiology, University of Turku, Turku, Finland.
    Alkio, Milla
    Laboratory of Animal Physiology, University of Turku, Turku, Finland; Poznan University of Medical Sciences, Poznań, Poland.
    Karikoski, Marika
    Faculty of Medicine University of Turku, Turku, Finland.
    Heinonen, Ilkka
    Halmstad University, School of Business, Innovation and Sustainability. Turku PET Centre University of Turku, Turku, Finland; Turku University Hospital, Turku, Finland.
    Anttila, Katja
    Laboratory of Animal Physiology, University of Turku, Turku, Finland.
    Melanoma Impairs Mouse Heart Function Which Short-Term Exercise Cannot Restore2022In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 36, no S1Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate whether melanoma impairs intrinsic heart function in mice and whether short-term voluntary running wheel exercise could reduce the possible negative effects. Additionally, we investigated whether changes in cell size, capillary density, calcium channel levels, metabolic enzyme activities or oxidative stress could explain the possible changes in heart function. Advanced melanoma has been shown to cause cardiac muscle wasting and influence heart function in vivo, we hypothesized that melanoma would also impair intrinsic heart function, which has not been investigated previously. We also hypothesized that voluntary short-term exercise could reduce the effects of melanoma on cardiac function since exercise training is known to improve cardiovascular function and reduce the negative effects of some cancers. Male mice were divided into untrained tumor-free group (control) and untrained melanoma group and trained melanoma group. The mice did voluntary running-wheel exercise until predetermined tumor size after which their hearts were isolated. The cardiac function was measured in retrograde perfusion at a constant pressure in multiple oxygen levels using Langendorff apparatus. The molecular and tissue level markers were measured afterwards. The melanoma animals were not cachectic as indicated lack of body weight loss. The rate of pressure production, pressure amplitude and rate of pressure decline were all significantly lower in the isolated hearts of the melanoma animals as compared to tumor-free animals. However, the heart function did not differ between the untrained and trained melanoma groups. Furthermore, there were no differences between the groups in the calcium channel levels, reactive oxygen species, catalase activity, lipid peroxidation or citrate synthase and lactate dehydrogenase activity. However, mice from both melanoma groups had significantly lower superoxide dismutase activity as compared to tumor-free animals, which might reduce the heart's ability to respond to possible changes in oxidative stress. Exercise trained animals had higher capillary density, but their cell size and heart weights did not significantly differ from the untrained groups. Running wheel exercise did not affect the final tumor growth either even though there was tendency at the beginning of the experiment that running wheel exercise could slow down the tumor growth. One reason for this could be that when melanoma proceeded, the mouse running activity reduced significantly. In conclusion, melanoma is an aggressive cancer that impairs intrinsic heart function even when no cachexia is present. The aggressiveness of melanoma also prevented the short-term voluntary exercise from alleviating the changes caused by melanoma. Future studies should combine the training to medical cancer treatment in order to estimate whether exercise training could be beneficial as adjunct therapy in melanoma treatment. © FASEB.

  • 21.
    Wheeler, Michael J
    et al.
    Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
    Green, Daniel J.
    Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia.
    Cerin, Ester
    Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia; School of Public Health, The University of Hong Kong, Hong Kong, China.
    Ellis, Kathryn A.
    Department of Psychiatry, University of Melbourne, Parkville, VIC, Australia.
    Heinonen, Ilkka
    Halmstad University, School of Business, Innovation and Sustainability, The Rydberg Laboratory for Applied Sciences (RLAS). Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia; Turku PET Centre, University of Turku, Turku, Finland.
    Lewis, Jaye
    Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia.
    Naylor, Louise H.
    Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia.
    Cohen, Neale
    Baker Heart and Diabetes Institute, 99 Commercial Rd, Melbourne, Victoria, Australia.
    Larsen, Robyn
    Baker Heart and Diabetes Institute, 99 Commercial Rd, Melbourne, Victoria, Australia.
    Dempsey, Paddy C.
    Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom; Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, United Kingdom.
    Kingwell, Bronwyn A.
    Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
    Owen, Neville
    Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Centre for Urban Transitions, Swinburne University of Technology, Hawthorn, Australia.
    Dunstan, David W.
    Cardiovascular Research Group, School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Perth, Australia Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Australia.
    Combined effects of continuous exercise and intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides in adults with obesity: a randomized crossover trial2020In: International Journal of Behavioral Nutrition and Physical Activity, E-ISSN 1479-5868, Vol. 17, no 1, article id 152Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Postprandial glucose, insulin, and triglyceride metabolism is impaired by prolonged sitting, but enhanced by exercise. The aim of this study was to assess the effects of a continuous exercise bout with and without intermittent active interruptions to prolonged sitting on postprandial glucose, insulin, and triglycerides.

    METHODS: Sedentary adults who were overweight to obese (n = 67; mean age 67 yr SD ± 7; BMI 31.2 kg∙m- 2 SD ± 4.1), completed three conditions: SIT: uninterrupted sitting (8-h, control); EX+SIT: sitting (1-h), moderate-intensity walking (30-min), uninterrupted sitting (6.5-h); EX+BR: sitting (1-h), moderate-intensity walking (30- min), sitting interrupted every 30-min with 3-min of light-intensity walking (6.5 h). Participants consumed standardized breakfast and lunch meals and blood was sampled at 13 time-points.

    RESULTS: When compared to SIT, EX+SIT increased total area under the curve (tAUC) for glucose by 2% [0.1-4.1%] and EX+BR by 3% [0.6-4.7%] (all p < 0.05). Compared to SIT, EX+SIT reduced insulin and insulin:glucose ratio tAUC by 18% [11-22%] and 21% [8-33%], respectively; and EX+BR reduced values by 25% [19-31%] and 28% [15-38%], respectively (all p < 0.001 vs SIT, all p < 0.05 EX+SIT-vs-EX+BR). Compared to SIT, EX+BR reduced triglyceride tAUC by 6% [1-10%] (p = 0.01 vs SIT), and compared to EX+SIT, EX+BR reduced this value by 5% [0.1-8.8%] (p = 0.047 vs EX+SIT). The magnitude of reduction in insulin tAUC from SIT-to-EX+BR was greater in those with increased basal insulin resistance. No reduction in triglyceride tAUC from SIT-to-EX+BR was apparent in those with high fasting triglycerides.

    CONCLUSIONS: Additional reductions in postprandial insulin-glucose dynamics and triglycerides may be achieved by combining exercise with breaks in sitting. Relative to uninterrupted sitting, this strategy may reduce postprandial insulin more in those with high basal insulin resistance, but those with high fasting triglycerides may be resistant to such intervention-induced reductions in triglycerides.

    TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry (ACTRN12614000737639 ).

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