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  • 1.
    Acerini, Carlo L.
    et al.
    University of Cambridge, England.
    Wac, Katarzyna
    University of Geneva, Switzerland.
    Bang, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lehwalder, Dagmar
    Merck KGaA, Germany.
    Optimizing Patient Management and Adherence for children receiving Growth Hormone2017In: Frontiers in Endocrinology, ISSN 1664-2392, E-ISSN 1664-2392, Vol. 8, article id 313Article in journal (Refereed)
    Abstract [en]

    Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360 degrees GH in Europe" meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many aspects of GH diseases. The three sessions, entitled "Short Stature Diagnosis and Referral," "Optimizing Patient Management," and "Managing Transition," each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patients journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on-going need for innovations.

  • 2.
    Agebratt, Christian
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 1, p. e0147149-Article in journal (Refereed)
    Abstract [en]

    Background

    Fruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.

    Objectives

    To study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.

    Methods

    Thirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.

    Results

    Weight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.

    Conclusions

    Although BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.

  • 3.
    Akesson, K.
    et al.
    Jonköping University, Sweden; Jonköping University, Sweden; Jonköping University, Sweden.
    Tompa, A.
    Jonköping University, Sweden; Jonköping University, Sweden.
    Ryden, A.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Novo Nordisk Inc, WA USA.
    Faresjo, M.
    Jonköping University, Sweden; Jonköping University, Sweden; Jonköping University, Sweden.
    Low expression of CD39(+)/CD45RA(+) on regulatory T cells (T-reg) cells in type 1 diabetic children in contrast to high expression of CD101(+)/CD129(+) on T-reg cells in children with coeliac disease2015In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 180, no 1, p. 70-82Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) and coeliac disease are both characterized by an autoimmune feature. As T1D and coeliac disease share the same risk genes, patients risk subsequently developing the other disease. This study aimed to investigate the expression of T helper (Th), T cytotoxic (Tc) and regulatory T cells (T-reg) in T1D and/or coeliac disease children in comparison to healthy children. Subgroups of T cells (Th:CD4(+) or Tc:CD8(+)); naive (CD27(+)CD28(+)CD45RA(+)CCR7(+)), central memory (CD27(+)CD28(+)CD45RA(-)CCR7(+)), effector memory (early differentiated; CD27(+)CD28(+)CD45RA(-)CCR7(-) and late differentiated; CD27(-)CD28(-)CD45RA(-)CCR7(-)), terminally differentiated effector cells (TEMRA; CD27(-)CD28(-)CD45RA(+)CCR7(-)) and T-reg (CD4(+)CD25(+)FOXP3(+)CD127(-)) cells, and their expression of CD39, CD45RA, CD101 and CD129, were studied by flow cytometry in T1D and/or coeliac disease children or without any of these diseases (reference group). Children diagnosed with both T1D and coeliac disease showed a higher percentage of TEMRA CD4(+) cells (Pless than005), but lower percentages of both early and late effector memory CD8(+) cells (Pless than005) compared to references. Children with exclusively T1D had lower median fluorescence intensity (MFI) of forkhead box protein 3 (FoxP3) (Pless than005) and also a lower percentage of CD39(+) and CD45RA(+) within the T-reg population (CD4(+)CD25(+)FOXP3(+)CD127(-)) (Pless than005). Children with exclusively coeliac disease had a higher MFI of CD101 (Pless than001), as well as a higher percentage of CD129(+) (Pless than005), in the CD4(+)CD25(hi) lymphocyte population, compared to references. In conclusion, children with combined T1D and coeliac disease have a higher percentage of differentiated CD4(+) cells compared to CD8(+) cells. T1D children show signs of low CD39(+)/CD45RA(+) T-reg cells that may indicate loss of suppressive function. Conversely, children with coeliac disease show signs of CD101(+)/CD129(+) T-reg cells that may indicate suppressor activity.

  • 4.
    Andelin, M.
    et al.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden..
    Kropff, J.
    Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands..
    Matuleviciene, V.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Joseph, J.I.
    Department of Anaesthesiology, Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, USA..
    Attvall, S.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    Theodorsson, Elvar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Hirsch, I.B.
    University of Washington, Seattle, WA, USA.
    Imberg, H.
    Statistiska Konsultgruppen, Gothenburg, Sweden..
    Dahlqvist, S.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden.
    Klonoff, D.
    Diabetes Research Institute, Mills-Peninsula Health Services, San Mateo, CA, USA..
    Haraldsson, B.
    Institute of Medicine, University of Gothenburg, Gothenburg, Sweden..
    DeVries, J.H.
    Department of Endocrinology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands..
    Lind, M.
    Department of Medicine, NU Hospital Group, Uddevalla, Sweden Institute of Medicine, University of Gothenburg, Gothenburg, Sweden lind.marcus@telia.com..
    Assessing the Accuracy of Continuous Glucose Monitoring (CGM) Calibrated With Capillary Values Using Capillary or Venous Glucose Levels as a Reference.2016In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 10, no 4, p. 876-884Article in journal (Refereed)
    Abstract [en]

    Background: Using the standard venous reference for the evaluation of continuous glucose monitoring (CGM) systems could possibly negatively affect measured CGM accuracy since CGM are generally calibrated with capillary glucose and venous and capillary glucose concentrations differ. We therefore aimed to quantify the effect of using capillary versus venous glucose reference samples on estimated accuracy in capillary calibrated CGM.less thanbr /greater thanMethods: We evaluated 41 individuals with type 1 diabetes mellitus (T1DM) using the Dexcom G4 CGM system over 6 days. Patients calibrated their CGM devices with capillary glucose by means of the HemoCue system. During 2 visits, capillary and venous samples were simultaneously measured by HemoCue and compared to concomitantly obtained CGM readings. The mean absolute relative difference (MARD) was calculated using capillary and venous reference samples.less thanbr /greater thanResults: Venous glucose values were 0.83 mmol/L (15.0 mg/dl) lower than capillary values over all glycemic ranges, P less than .0001. Below 4 mmol/l (72 mg/dl), the difference was 1.25 mmol/l (22.5 mg/dl), P = .0001, at 4-10 mmol/l (72-180 mg/dl), 0.67 mmol/l (12.0 mg/dl), P less than .0001 and above 10 mmol/l (180 mg/dl), 0.95 mmol/l (17.1 mg/dl), P less than .0001. MARD was 11.7% using capillary values as reference compared to 13.7% using venous samples, P = .037. Below 4 mmol/l (72 mg/dl) MARD was 16.6% and 31.8%, P = .048, at 4-10 mmol/l (72-180 mg/dl) 12.1% and 12.6%, P = .32, above 10 mmol/l (180 mg/dl) 8.7% and 9.2%, P = .82.less thanbr /greater thanConclusion: Using capillary glucose concentrations as reference to evaluate the accuracy of CGM calibrated with capillary samples is associated with a lower MARD than using venous glucose as the reference. Capillary glucose concentrations were significantly higher than venous in all glycemic ranges.less thanbr /greater than (© 2016 Diabetes Technology Society.)

  • 5.
    Andreas, Svensson
    Linköping University, Department of Electrical Engineering, Automatic Control. Linköping University, The Institute of Technology.
    Model Predictive Control with Invariant Sets in Artificial Pancreas for Type 1 Diabetes Mellitus2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    This thesis deals with Model Predictive Control (MPC) for artificial pancreas for Type 1 Diabetes Mellitus patients. A control strategy exploiting invariant sets in MPC for blood glucose level control is developed, to the authors knowledge for the first time. The work includes various types of invariant sets relevant for the artificial pancreas problem, and different ways to incorporate them into the MPC strategy. The work is an extension to the zone MPC controller for artificial pancreas developed at University of California Santa Barbara and Sansum Diabetes Research Institute.

    The evaluation of the proposed control strategy is done in silico in the U.S. Food and Drug Administration approved metabolic simulator. The trials show some promising results in terms of more rapid meal responses and decreased variability between the subjects than the zone MPC. An attempt to robust control employing invariant sets proved to be less promising in the evaluations. The results indicate that the direct application of known robust control techniques is not appropriate, and that more appropriate robust control techniques must be searched for, or developed, more specific to the artificial pancreas control.

    Altogether, this thesis pinpoints a possible future direction of artificial pancreas control design, with MPC based on invariant sets.

  • 6.
    Beam, Craig A.
    et al.
    Western Michigan University, MI 49008 USA.
    MacCallum, Colleen
    Western Michigan University, MI 49008 USA.
    Herold, Kevan C.
    Yale University, CT USA; Yale University, CT USA.
    Wherrett, Diane K.
    Hospital Sick Children, Canada; University of Toronto, Canada.
    Palmer, Jerry
    University of Washington, WA 98195 USA; VA Puget Sound Health Care Syst, WA USA.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 1, p. 43-49Article in journal (Refereed)
    Abstract [en]

    GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). We estimate that there is a 98% probability that 20 mu g GAD with alum administered twice yields a positive biological effect. The effect is probably a 15-20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between -0.250 and -0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of -0.294 pmol/ml at 1 year for untreated newly diagnosed patients. The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.

  • 7.
    Birkebaek, N. H.
    et al.
    Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
    Drivvoll, A K
    Norwegian Childhood Diabetes Registry, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
    Aakeson, K.
    Department of Pediatrics, County Hospital Ryhov, Jönköping, Sweden.
    Bjarnason, R.
    Medical Center, Landspitali University Hospital, Reykjavik, Iceland; Department of Pediatrics, University of Iceland, Reykjavik, Iceland.
    Johansen, A.
    Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Skrivarhaug, T.
    Norwegian Childhood Diabetes Registry, Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
    Thorsson, A. V.
    Medical Center, Landspitali University Hospital, Reykjavik, Iceland; Department of Pediatrics, University of Iceland, Reykjavik, Iceland.
    Svensson, J.
    Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Children and Adolescents, Copenhagen University Hospital, Herlev, Denmark.
    Incidence of severe hypoglycemia in children with type 1 diabetes in the Nordic countries in the period 2008-2012: association with hemoglobin A 1c and treatment modality2017In: BMJ Open Diabetes Research & Care, ISSN 2052-4897, Vol. 5, no 1, article id e000377Article in journal (Refereed)
    Abstract [en]

    Treatment of type 1 diabetes has been intensified aiming at normalizing blood glucose, which may increase the risk of severe hypoglycemia (SH). We aimed to compare the incidence of SH events in the four Nordic countries Denmark, Iceland, Norway and Sweden, and to assess the influence of hemoglobin A1c (HbA1c) and treatment modalities on the frequency of SH; particularly, to explore if a HbA1c target =6.7% (50 mmol/mol) is feasible.

  • 8.
    Bjarnegård, Niclas
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Faculty of Health Sciences.
    Aspects on wall properties of the brachial artery in man: with special reference to SLE and insulin-dependent diabetes mellitus2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The mechanical properties of the arterial wall are of great importance for blood pressure regulation and cardiac load. With increasing age, large arteries are affected by increased wall stiffness. Furthermore, atherosclerotic manifestations may increase the stiffness even further, both processes acting as independent cardiovascular risk factors affecting the arterial system in a heterogeneous way.

    The aims of this thesis was to characterize the local mechanical properties of brachial artery (BA) with the aid of ultrasound technique and to evaluate the influence of 1) age, gender, sympathetic stimulation and examination site; 2) type 1 diabetes (DM) and its association to circulatory biomarkers; and 3) to evaluate the general properties of the arterial system with the aid of pulse wave velocity (PWV) as well as pulse wave analysis (PWA) in systemic lupus erythematosus (SLE) and correlate the findings to disease activity and circulatory biomarkers.

    In the most proximal arterial segment of the upper arm a pronounced age-related decrease in wall distensibility, increase in intima-media thickness (IMT), and a slight increase in diameter were seen. Sympathetic stimulation had no influence on wall mechanics. More distally in BA, no change in diameter, and only minor increase in IMT and decrease in distensibility were seen. No gender differences were found. These findings suggest that the principle transit zone between elastic and muscular artery behaviour is located in the proximal part of the upper arm.

    Women with uncomplicated insulin-dependent DM had similar diameter, IMT and distensibility in their distal BA as controls, whereas flow-mediated dilatation (FMD) was slightly, and nitrate mediated dilatation (NMD) markedly reduced. NMD was negatively correlated with higher HbA1c levels. Vascular smooth muscle cell function seems to be an early manifestation of vascular disease in women with DM, influenced by long-term hyperglycaemia.

    Women with SLE had increased aortic PWV compared to controls, a finding positively associated with increased levels of complement factor 3 (C3), but not with disease activity. The increased stiffness of central arteries may be one factor contributing to the increased cardiovascular risk seen in SLE.

    List of papers
    1. Age affects proximal brachial artery stiffness: differential behaviour within the length of the brachial artery?
    Open this publication in new window or tab >>Age affects proximal brachial artery stiffness: differential behaviour within the length of the brachial artery?
    Show others...
    2003 (English)In: Ultrasound in Medicine and Biology, ISSN 0301-5629, Vol. 29, no 8, p. 1115-1121Article in journal (Refereed) Published
    Abstract [en]

    With increasing age, the diameter of central elastic arteries increases, whereas their distensibility decreases. The purpose of this study was to investigate the mechanical properties of the proximal brachial artery in relation to age and gender. Distensibility coefficient (DC), stiffness and compliance coefficient (CC) were calculated in 136 healthy males and females (range 9-82 y) using echo-tracking sonography. CC decreased with age in both genders, but CC was higher in males. Stiffness increased and DC decreased with age in an exponential manner, without any differences between genders. In conclusion, as in central elastic arteries, the distensibility of the proximal brachial artery decreases with age, in contrast to earlier reports on the muscular distal brachial artery. This may imply that the transition between elastic and muscular artery behavior is within the length of the brachial artery. In future studies using the brachial artery, the examination site needs to be defined.

    Keywords
    Brachial artery, Ageing, Gender, Echo-tracking, Distensibility, Stiffness
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13028 (URN)10.1016/S0301-5629(03)00052-8 (DOI)
    Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2017-03-27
    2. The effect of sympathetic stimulation on proximal brachial artery mechanics in humans: differential behaviour within the length of the brachial artery
    Open this publication in new window or tab >>The effect of sympathetic stimulation on proximal brachial artery mechanics in humans: differential behaviour within the length of the brachial artery
    2004 (English)In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 182, no 1, p. 21-27Article in journal (Refereed) Published
    Abstract [en]

    Aims: The mechanical properties of arteries play a major role in the regulation of blood pressure and cardiac performance. The effect of sympathetic stimulation on the mechanical properties of the proximal brachial artery was analysed in 18 healthy volunteers, nine young (25 ± 2 years) and nine elderly (69 ± 2 years).

    Methods: A non-invasive ultrasonic echo-tracking system for measurement of systolic/diastolic variation of the proximal brachial artery diameter in combination with intra-arterial pressure measurements was used to determine wall mechanics. The pressure–diameter (P–D) relationship, distensibility coefficient (DC), compliance coefficient (CC) and stiffness(β) were obtained at rest and during sympathetic stimulation induced by lower body negative pressure (LBNP).

    Results: The peripheral vascular resistance increased by 100 and 72%, respectively in the young and elderly during LBNP (P < 0.001). Simultaneously, the mechanical properties of the proximal brachial artery remained unaltered, as estimated from both P–D relationship and stiffness in young (β-index rest: 5.2 ± 0.9, LBNP: 5.5 ± 1.3, NS) as well as elderly (β-index rest: 13.6 ± 4.6, LBNP: 16.1 ± 4.7, NS).

    Conclusions: LBNP-induced sympathetic activation does not change proximal brachial artery mechanics, in contrast to earlier reports on the muscular distal brachial artery. This may imply that the transition between elastic and muscular artery behaviour is within the length of the brachial artery, where the site of transition from elastic to muscular wall structure needs to be specified in future studies.

    Keywords
    ageing, brachial artery, distensibility, lower body negative pressure, stiffness, sympathetic stimulation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13029 (URN)10.1111/j.1365-201X.2004.01336.x (DOI)
    Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2018-05-24
    3. Increased aortic pulse wave velocity in middle-aged women with systemic lupus erythematosus
    Open this publication in new window or tab >>Increased aortic pulse wave velocity in middle-aged women with systemic lupus erythematosus
    Show others...
    2006 (English)In: Lupus, ISSN 0961-2033, Vol. 15, no 10, p. 644-650Article in journal (Refereed) Published
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a connective tissue disease where inflammatory activity affects several organ systems. An increased risk of cardiovascular disease has been identified in these patients, even after correction for traditional risk factors. The aim of the present study was to evaluate arterial stiffness and central hemodynamics in women with SLE in comparison to controls.

    Arterial tonometry was used to measure aortic (carotid-femoral) and arm (carotid-radial) pulse wave velocity (PWV), reflected pressure waves, and aortic augmentation index (AIx) in 27 women with SLE (52 to 68 years) and 27 controls. Aortic PWV was higher in women with SLE than controls, 9.8 m/s versus 8.2 m/s (P 0.01), after correction for mean arterial pressure and body mass index, 9.5 m/s versus 8.5 m/s (P 0.05). Other parameters were similar, arm PWV, 8.4 versus 8.5 m/s, AIx 34 versus 33% and calculated central aortic pulse pressure 48 versus 43 mmHg, in SLE and controls, respectively (NS). Aortic PWV was positively associated to C-reactive protein (CRP) and complement factor 3 (C3).

    Women with SLE have increased stiffness of their elastic central arteries. This may be one factor contributing to the increased cardiovascular risk seen in this cohort.

    Keywords
    arteries, blood pressure, elasticity, pulse, SLE, women
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13030 (URN)10.1177/0961203306071402 (DOI)
    Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2017-03-27
    4. Impaired endothelial independent vasodilatation in women with type 1 diabetes
    Open this publication in new window or tab >>Impaired endothelial independent vasodilatation in women with type 1 diabetes
    Show others...
    2008 (English)Manuscript (preprint) (Other academic)
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-13031 (URN)
    Available from: 2008-03-13 Created: 2008-03-13 Last updated: 2017-03-27Bibliographically approved
  • 9.
    Björn, Anders
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, Faculty of Science & Engineering.
    HbA1c according to different standards2016Other (Other (popular science, discussion, etc.))
  • 10.
    Björn, Anders
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, Faculty of Science & Engineering.
    HbA1c enligt olika standarder2016Other (Other (popular science, discussion, etc.))
  • 11.
    Björn, Anders
    Linköping University, Department of Mathematics, Mathematics and Applied Mathematics. Linköping University, Faculty of Science & Engineering.
    HbA1c podle různých standardů;2016Other (Other (popular science, discussion, etc.))
  • 12.
    Brismar, T. B.
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Shams, S.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Berinder, K.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Berlin, M.
    Karolinska University Hospital, Sweden.
    Udden, J.
    Karolinska University Hospital, Sweden.
    Brismar, K.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Ringertz, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    GLUCOCORTICOIDS AND SARCOIDOSIS: A LONGITUDINAL STUDY ON THE EFFECTS ON CORTICAL AND TRABECULAR BONE2015In: Sarcoidosis Vasculitis and Diffuse Lung Diseases, ISSN 1124-0490, Vol. 32, no 1, p. 63-69Article in journal (Refereed)
    Abstract [en]

    Background: Glucocorticoid induced osteoporosis is a well-known side effect of glucocorticoid treatment. In sarcoidosis the impact on bone by glucocorticoid treatment is complex due to hormonal disturbances of calcium and vitamin-D, which by itself may cause bone loss. In this study we aimed to investigate the longitudinal impact of glucocorticoids on cortical and trabecular bone in patients with mild, recently diagnosed sarcoidosis.

    Methods: Ten patients (8 females; mean age 44 (+/- 13)) were studied during one year of glucocorticoid treatment. The assessment of mainly cortical to purely trabecular bone was made by dual X-ray absorptiometry (DXA) of the spine and hip, quantitative ultrasound of the calcaneus, and magnetic resonance relaxometry of the spine and calcaneus. Bone and hormonal measurements were performed at baseline, after 3, 6, and 12 months, and baseline, 3 weeks and 3 months, respectively.

    Results: DXA of the spine, decreased from baseline at 6 months (P=0.01). R2 of the calcaneus decreased with time (B: -3.6; P=0.03). In the females (n=8) there was a significant decrease in DXA of the spine when comparing 3 months and 6 months (P=0.03), and 3 months and 12 months (P=0.02) and a decrease in R2 of the calcaneus from baseline to 12 months (P=0.01). There was no change in hormonal levels.

    Conclusion: Treatment of initial mild sarcoidosis with dose tapered glucocorticoid therapy only mildly affects the final trabecular and cortical bone and hormone levels. Dose tapering is an important part in glucocorticoid therapy, likely contributing to the mild effects on bone observed in this study.

  • 13.
    Carlhäll, Sara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Brynhildsen, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Claesson, Ing-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Josefsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Sydsjö, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Thorsell, Annika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Blomberg, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
    Maternal obesity (Class I-III), gestational weight gain and maternal leptin levels during and after pregnancy: a prospective cohort study2016In: BMC Obesity, ISSN 2052-9538, Vol. 3, no 28Article in journal (Refereed)
    Abstract [en]

    Background

    Maternal obesity is accompanied by maternal and fetal complications during and after pregnancy. The risks seem to increase with degree of obesity. Leptin has been suggested to play a role in the development of obesity related complications. Whether maternal leptin levels differ between obese and morbidly obese women, during and after pregnancy, have to our knowledge not been previously described. Neither has the association between maternal leptin levels and gestational weight gain in obese women. The aim was to evaluate if maternal plasma leptin levels were associated with different degrees of maternal obesity and gestational weight gain.

    Methods

    Prospective cohort study including women categorized as obesity class I-III (n = 343) and divided into three gestational weight gain groups (n = 304). Maternal plasma leptin was measured at gestational week 15, 29 and 10 weeks postpartum. Maternal Body Mass Index (BMI) was calculated from early pregnancy weight. Gestational weight gain was calculated using maternal weight in delivery week minus early pregnancy weight. The mean value and confidence interval of plasma-leptin were analysed with a two-way ANOVA model. Interaction effect between BMI and gestational weight gain group was tested with a two-way ANOVA model.

    Results

    The mean maternal leptin concentrations were significantly higher in women with obesity class III compared to women in obesity class I, at all times when plasma leptin were measured. The mean leptin concentrations were also significantly higher in women with obesity class II compared to women in obesity class I, except in gestational week 29. There was no difference in mean levels of plasma leptin between the gestational weight gain groups. No significant interaction between BMI and gestational weight gain group was found.

    Conclusions

    Plasma leptin levels during and after pregnancy were associated with obesity class but not with degree of gestational weight gain. These results are in concordance with epidemiological findings where the risk of obstetric complications increases with increased maternal obesity class. The effect on obstetric outcome by degree of gestational weight gain is less pronounced than the adverse effects associated with maternal obesity.

  • 14.
    Chisalita, Simona Ioana
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Eson Jennersjö, Pär
    Borensberg Health Centre, Linköping.
    Paulsson, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Westermark, Gunilla
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Olsson, Anders
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Arnqvist, Hans
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Differential lipid profile and hormonal response in type 2 diabetes by exogenous insulin aspart versus the insulin secretagogue repaglinide, at the same glycemic control2009In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 46, no 1, p. 35-42Article in journal (Refereed)
    Abstract [en]

    Our aim was to study, at the same glycemic control, how treatment with either the insulin secretagogue repaglinide or exogenous insulin aspart affects endogenous insulin secretion, plasma insulin and IAPP (islet amyloid polypeptide) levels, GH-IGF (growth hormone-insulin-like growth factor) axis and plasma lipoprotein concentrations in patients with type 2 diabetes. Five patients, age 65.0 +/- A 4.1 years (mean +/- A SE), body weight 82.5 +/- A 5.0 kg, BMI (body mass index) 27.7 +/- A 1.5 kg/m(2) were treated for 10 weeks with repaglinide or insulin aspart in a randomized, cross-over study. At the end of each treatment a 24-h metabolic profile was performed. Blood glucose, C-peptide, free human insulin, free total (human and analogue) insulin, proinsulin, IAPP, IGF-I, IGFBP-1 (IGF binding protein-1), GHBP (growth hormone binding protein) and plasma lipoprotein concentrations were measured. Similar 24-h blood glucose profiles were obtained with repaglinide and insulin aspart treatment. During the repaglinide treatment, the meal related peaks of C-peptide and free human insulin were about twofold higher than during treatment with insulin aspart. Proinsulin, GHBP were higher and IAPP levels tended to be higher during repaglinide compared to insulin aspart. Postprandial plasma total cholesterol, triglycerides and apolipoprotein B concentrations were higher on repaglinide than on insulin aspart treatment. Our results show that, at the same glycemic control, treatment with exogenous insulin aspart in comparison with the insulin secretagogue repaglinide result in a lower endogenous insulin secretion, and a tendency towards a less atherogenic postprandial lipid profile.

  • 15.
    Dahlqvist, Per
    et al.
    Norrlands Universitetssjukhus, Umeå .
    Bensing, Sophie
    Karolinska universitetssjukhuset, Solna .
    Ekwall, Olov
    Drottning Silvias barn- och ungdomssjukhus, Göteborg .
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Bergthorsdottir, Ragnhildur
    Sahlgrenska sjukhuset, Göteborg .
    Hulting, Anna-Lena
    Karolinska universitetssjukhuset, Solna .
    [A national medical emergency card for adrenal insufficiency. A new warning card for better management and patient safety].2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 44, p. 2226-2227Article in journal (Other academic)
  • 16.
    Dalin, Frida
    et al.
    Karolinska Institutet, Stockholm, Sweden, Uppsala University, Uppsala, Sweden.
    Nordling Eriksson, Gabriel
    Karolinska Institutet, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå University, Umeå, Sweden.
    Hallgren, Åsa
    Karolinska Institutet, Stockholm, Sweden.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Endocrinology. Linköping University, Faculty of Medicine and Health Sciences.
    Ekwall, Olov
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Söderberg, Stefan
    Umeå University, Umeå, Sweden.
    Rönnelid, Johan
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Olcén, Per
    Örebro University, Örebro, Sweden.
    Winqvist, Ola
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Kriström, Berit
    Umeå University, Umeå, Sweden.
    Laudius, Maria
    Umeå University, Umeå, Sweden.
    Isaksson, Magnus
    Uppsala University, Uppsala, Sweden.
    Halldin Stenlid, Maria
    Uppsala University, Uppsala, Sweden.
    Gustafsson, Jan
    Uppsala University, Uppsala, Sweden.
    Gebre-Medhin, Gennet
    Uppsala University, Uppsala, Sweden.
    Björnsdottir, Sigridur
    Karolinska In Karolinska University Hospital, Stockholm, Sweden.
    Janson, Annika
    Karolinska Institutet, Stockholm, Sweden.
    Åkerman, Anna-Karin
    Örebro University, Örebro, Sweden.
    Åman, Jan
    Örebro University, Örebro, Sweden.
    Duchen, Karel
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Bergthorsdottir, Ragnhildur
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Johannsson, Gudmundur
    Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lindskog, Emma
    The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Landin-Olsson, Mona
    Skåne University Hospital, Malmö, Sweden..
    Elfving, Maria
    Lund University, Lund, Sweden..
    Waldenström, Erik
    Skåne University Hospital, Malmö, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Stockholm, Sweden.
    Kämpe, Olle
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Bensing, Sophie
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Clinical and immunological characteristics of Autoimmune Addison's disease: a nationwide Swedish multicenter study.2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 2, p. 379-389Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.

    OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.

    DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.

    MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.

    RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).

    CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.

  • 17.
    de Seymour, Jamie V.
    et al.
    Univ Auckland, New Zealand.
    Tu, Stephanie
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Univ Auckland, New Zealand.
    He, Xiaoling
    Chongqing Med Univ, Peoples R China.
    Zhang, Hua
    Chongqing Med Univ, Peoples R China.
    Han, Ting-Li
    Univ Auckland, New Zealand; Chongqing Med Univ, Peoples R China.
    Baker, Philip N.
    Univ Auckland, New Zealand; Chongqing Med Univ, Peoples R China; Univ Leicester, England.
    Sulek, Karolina
    Univ Auckland, New Zealand; Univ Copenhagen, Denmark.
    Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy2018In: Metabolomics, ISSN 1573-3882, E-ISSN 1573-3890, Vol. 14, no 6, article id 79Article in journal (Refereed)
    Abstract [en]

    Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms. Investigate the maternal hair metabolome for predictive biomarkers of ICP. The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography-mass spectrometry. Of 105 metabolites detected in hair, none were significantly associated with ICP. Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

  • 18.
    Ekman, Bertil
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Alstrand, N
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences. County Hospital, Kalmar .
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Jenmalm, Maria C
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Altered Chemokine Th1/Th2 Balance in Addison's Disease: Relationship with Hydrocortisone Dosing and Quality of Life2014In: Hormone and Metabolic Research, ISSN 0018-5043, E-ISSN 1439-4286, Vol. 46, no 1, p. 48-53Article in journal (Refereed)
    Abstract [en]

    The adrenalitis found in autoimmune Addison’s disease (AAD) is considered having a Th1-driven pathogenesis. Circulating Th1- and Th2-associated chemokines responsible for the trafficking of leukocytes to inflammatory sites are markers for the Th1/Th2 balance. The aim of the study was to assess if the same daily hydrocortisone dose of 30 mg given in either 2 or 4 doses to patients with AAD could affect the Th1/Th2 balance of circulating chemokines.

    Fifteen patients (6 women) with AAD were included in this randomised, placebo controlled, double blind cross-over study. Samples for chemokines, Th1-associated (CXCL10, CXCL11) and Th2-associated (CCL17, CCL22), were drawn 5 times during a 24-h period at the end of each treatment period and analysed with Luminex. Seven control subjects did the same diurnal blood sampling once. Subjects with AAD had higher median diurnal levels of the Th1-associated chemokines than controls, CXCL10 [43 (33–56) pg/ml vs. 22 (19–34) pg/ml, p<0.01] and CXCL11 [37 (29–48) pg/ml vs. 16 (9–24) pg/ml, p<0.001], whereas no significant difference was found regarding the Th2-related chemokines. Similar chemokine levels were found when the same hydrocortisone dose of 30 mg was divided in 2 or 4 doses. Levels of CXCL11 correlated negatively with scores of SF-36 domains (high score indicate better health) of General Health (GH) and total score for Physical Component Summary (PCS), and these negative correlations were most pronounced at 04:00 h on the 2-dose regimen. Patients with AAD have a dominant Th1 chemokine profile that partially correlates to reduced quality of life.

  • 19.
    Enander, Rebecka
    et al.
    SkaS Hosp Grp, Sweden.
    Adolfsson, Peter
    Hosp Halland, Sweden; Univ Gothenburg, Sweden.
    Bergdahl, Torun
    SkaS Hosp Grp, Sweden.
    Forsander, Gun
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Hanas, Ragnar
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Beta cell function after intensive subcutaneous insulin therapy or intravenous insulin infusion at onset of type 1 diabetes in children without ketoacidosis2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 6, p. 1079-1085Article in journal (Refereed)
    Abstract [en]

    Background

    Our aim was to see if IV insulin therapy at diagnosis preserves beta‐cell function better than multiple subcutaneous (SC) injections.

    Methods

    Fifty‐four children 9.9 ± 3.5 years (range 2.8‐14.9) without ketoacidosis were included in a 2 years, randomized multicenter study with insulin SC or 48 to 72 hours IV initially. Thirty‐three (61%) were boys, 22 (41%) were pubertal. Forty‐eight subjects completed 12 months follow‐up and 43 completed 24 months. At 1, 6, 12, and 24 months, hemoglobin A1c (HbA1c), C‐peptide and insulin/kg/24 h were measured. At 24 months, a mixed‐meal tolerance test (MMTT) was performed.

    Results

    HbA1c at diagnosis was 10.7%, (93 mmol/mol) for IV, 10.7%, (94 mmol/mol) for SC. During the first 2 full days of insulin therapy, mean plasma glucose was 8.2 mmol/L for IV, 9.5 for SC (P = .025). Mean insulin dose was 1.5 U/kg/d for IV vs 1.0 for SC (P = .001). Sixteen (7 in IV, 9 in SC group) started with insulin pumps during the follow‐up. At 24 months, we saw no significant differences: HbA1c (7.5%, 58 mmol/mol, for IV, 7.2%, 55 mmol/mol, for SC; ns), insulin doses (0.79 vs 0.88 U/kg/d; ns), fasting C‐peptide (0.08 vs 0.12 nmol/L; ns), maximal MMTT response (0.19 vs 0.25 nmol/L; ns) and AUC (18.26 vs 23.9 nmol/L*min; ns). Peak C‐peptide >0.2 nmol/L in the combined IV and SC groups correlated significantly with HbA1c and C‐peptide at onset in a multiple regression.

    Conclusion

    Residual beta cell function at 2 years seems to be independent from initial insulin regimens but related to HbA1c and C‐peptide at onset.

  • 20.
    Eriksson, Daniel
    et al.
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm, Sweden.
    Dalin, Frida
    Karolinska Institutet, Stockholm, Uppsala University, Uppsala, Sweden.
    Eriksson, Gabriel Nordling
    Karolinska Institutet, Stockholm, Sweden.
    Landegren, Nils
    Karolinska Institutet, Stockholm, Sweden, Uppsala University, Uppsala, Sweden.
    Bianchi, Matteo
    Uppsala University, Uppsala, Sweden.
    Hallgren, Åsa
    Karolinska Institutet, Stockholm, Uppsala University, Uppsala, Sweden.
    Dahlqvist, Per
    Umeå University, Umeå, Sweden.
    Wahlberg, Jeanette
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Ekwall, Olov
    Sahlgrenska Academy, University of Gothenburg, Gothenburg.
    Winqvist, Ola
    Karolinska Institutet, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Institutet, Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala University, Uppsala, Sweden.
    Hulting, Anna-Lena
    Karolinska Institutet, Stockholm, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala University, Uppsala, Sweden, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
    Alimohammadi, Mohammad
    Uppsala University, Uppsala, Sweden.
    Husebye, Eystein S
    Karolinska Institutet, Stockholm, University of Bergen, Bergen, K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway.
    Knappskog, Per Morten
    University of Bergen, Bergen, Haukeland University Hospital, Bergen, Norway.
    Rosengren Pielberg, Gerli
    Uppsala University, Uppsala, Sweden.
    Bensing, Sophie
    Karolinska University Hospital, Stockholm, Karolinska Institutet, Stockholm, Sweden.
    Kämpe, Olle
    Karolinska Institutet, Stockholm, Karolinska University Hospital, Stockholm, Uppsala University, Uppsala, Sweden, K.G. Jebsen Center for Autoimmune Disorders, Bergen, Norway.
    Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1.2018In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, no 1, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.

    Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.

    Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.

    Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.

    Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.

  • 21.
    Erlingsson, Styrbjörn
    et al.
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Herard, Sebastian
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Thoracic and Vascular Surgery.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Nyström, Fredrik
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences.
    Men develop more intraabdominal obesity and signs of the metabolic syndrome after hyperalimentation than women2009In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 58, no 7, p. 995-1001Article in journal (Refereed)
    Abstract [en]

    We prospectively studied the effects of fast food-based hyperalimentation on insulin sensitivity and components of the metabolic syndrome and analyzed this with respect to sex. Twelve nonobese men and 6 nonobese women (26 +/- 6.6 years old), and an age-matched control group were recruited. Subjects in the intervention group aimed for 5% to 15% weight increase by doubling their regular caloric intake based on at least 2 fast food meals a day while also adopting a sedentary lifestyle for 4 weeks (andlt;5000 steps a day). Weight of Subjects in the intervention group increased from 67.6 +/- 9.1 to 74.0 +/- 11 kg (P andlt;.001), with no sex difference with regard to this or with respect to changes of total abdominal fat volumes or waist circumferences. Fasting insulin (men: before, 3.8 +/- 1.7 mu U/mL, after, 7.4 +/- 3.1 mu U/mL; P=.004; women: before, 4.9 +/- 2.3 mu U/mL; after, 5.9 +/- 2.8 mu U/mL; P =.17), systolic blood pressure (men: before, 117 +/- 13 mm Hg; after, 127 +/- 9.1 mm Hg; P =.002; women: before, 102 +/- 5.1 mm Hg; after, 98 +/- 5.4 mm Hg; P =.39), serum low-density lipoprotein cholesterol, and apolipoprotein B increased only in the men of the intervention group. The sex differences in the metabolic responses to the intervention were linked to a considerable difference in the fat accumulation pattern; 41.4% +/- 9.2% of the increase of the fat volume in the abdominal region was accumulated intraabdominally in men and 22.7 +/- 6.5% in women (P andlt;.0001). This Study thus showed that women are protected, compared with men, against developing intraabdominal obesity when adopting a standardized obesity-provoking lifestyle. Our findings suggest that it is not different lifestyles and/or behaviors that underlie the fact that men have a higher cardiovascular risk at the same level of percentage of body fat than women.

  • 22.
    E:son Jennersjö, Pär
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Risk factors in type 2 diabetes with emphasis on blood pressure, physical activity and serum vitamin D2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Type 2 diabetes is a common chronic disease with a two-fold increased risk for cardiovascular morbidity and mortality and has an increasing prevalence worldwide. This thesis is based on a study conducted in primary health care in Östergötland and Jönköping, Sweden. The aim of the thesis was to evaluate new risk markers to identify patients with high risk of developing cardiovascular disease in middle-aged men and women with type 2 diabetes.

    Methods

    Data from the cohort study CArdiovascular Risk in type 2 DIabetes – a Prospective study in Primary care (CARDIPP) was used. In paper III data were also used from CARDIPP-Revisited where all participants in the CARDIPP study were invited four years after the baseline investigation for a re-investigation. In paper IV data were used from CAREFUL which is a control group of 185 subjects without diabetes. The investigation included a standard medical history including data on diabetes duration and on-going medication. Anthropometric data were recorded and both office and ambulatory blood pressure were measured. The patients filled out a detailed questionnaire and physical activity was measured by using waist-mounted pedometers. Pedometer-determined physical activity was classified in four groups: Group 1: <5000 steps/day (‘sedentary’); Group 2: 5000-7499 steps/day (‘low active’); Group 3: 7500-9999 steps/day (‘somewhat active’); Group 4: and ≥10 000 steps/day (‘active’). Blood samples were drawn for routine analyses and also frozen for later analyses. The investigations at the departments of physiology included echocardiography, measurements of the carotid intima-media thickness, applanation tonometry and measurements of  sagittal abdominal diameter.

    Results

    Paper 1:

    Patients with a non-dipping systolic blood pressure pattern showed higher left ventricular mass index and pulse wave velocity (PWV) compared with patients with ≥10% decline in nocturnal systolic blood pressure. Patients with <10% decline in nocturnal systolic blood pressure had higher BMI and sagittal abdominal diameter, lower GFR and higher albumin:creatinine ratio and also higher levels of NT-proBNP than patients with a dipping pattern of the nocturnal blood pressure.

    Paper 2:

    The number of steps/day were inversely significantly associated with BMI, waist circumference and sagittal abdominal diameter, levels of CRP, levels of interleukin-6 and PWV.

    Paper 3:

    At the 4-year follow-up the change in PWV (ΔPWV) from baseline was calculated. The group with the lowest steps/day had a significantly higher increase in ΔPWV compared with the group with the highest steps/day. The associations between baseline steps/day and ΔPWV remained after further adjustment in a multivariate linear regression statistically significant (p=0.005). 23% of the variation in the study could be explained by our model. Every 1000 extra steps at baseline reduced the change in ΔPWV by 0.103 m/s between baseline and follow-up.

    Paper 4:

    Low vitamin D levels were associated with significantly increased risk for premature mortality in men with type 2 diabetes. High levels of parathyroid hormone were associated with significantly increased risk for premature mortality in women with type 2 diabetes. These relationships were still statistically significant also when two other well-established risk markers for mortality, PWV and carotid intima-media thickness, were added to the analyses.

    Conclusions

    Ambulatory blood pressure recording can by addressing the issue of diurnal blood pressure variation, explore early cardiovascular organ damage and microvascular complications that goes beyond effects of standardised office blood pressure measurements. Pedometer-determined physical activity may serve as a surrogate marker for inflammation and subclinical organ damage in patients with type 2 diabetes. There is novel support for the durable vascular protective role of a high level of daily physical activity, which is independent of BMI and systolic blood pressure. The use of pedometers is feasible in clinical practice and provides objective information not only about physical activity but also the future risk for subclinical organ damage in middle-aged people with type 2 diabetes. Our results indicate that low vitamin D levels in men or high parathyroid hormone levels in women give independent prognostic information of an increased risk for total mortality.

    List of papers
    1. Circadian blood pressure variation in patients with type 2 diabetes - relationship to macro- and microvascular subclinical organ damage
    Open this publication in new window or tab >>Circadian blood pressure variation in patients with type 2 diabetes - relationship to macro- and microvascular subclinical organ damage
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    2011 (English)In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 5, no 3, p. 167-173Article in journal (Refereed) Published
    Abstract [en]

    Aims

    To explore the association between nocturnal blood pressure (BP) dipper status and macro- and microvascular organ damage in type 2 diabetes.

    Methods

    Cross-sectional data from 663 patients with type 2 diabetes, aged 55–66 years, were analysed. Nurses measured office BP and ambulatory BP during 24 h. Individuals with ≥10% difference in nocturnal systolic blood pressure (SBP) relative to daytime values were defined as dippers. Non-dippers were defined as <10% nocturnal decrease in SBP. Estimated glomerular filtration rate (GFR) was calculated and microalbuminuria was measured by albumin:creatinine ratio (ACR). Aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries.

    Results

    We identified 433 dippers and 230 subjects with a nocturnal non-dipping pattern. Nocturnal SBP dipping was independently of office SBP associated with decreased PWV (p = 0.008), lower ACR (p = 0.001) and NT-proBNP (p = 0.001) and increased GFR (p < 0.001).

    Conclusions

    We conclude that diurnal BP variation provides further information about early macro- and microvascular subclinical organ damage that goes beyond standardized office BP measurements in patients with type 2 diabetes.

    Place, publisher, year, edition, pages
    Elsevier, 2011
    Keywords
    Type 2 diabetes mellitus ambulatory blood pressure arterial stiffness microalbuminuria diurnal blood pressure variation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-75571 (URN)10.1016/j.pcd.2011.04.001 (DOI)000304279600004 ()
    Note

    funding agencies|Medical Research Council of Southeast Sweden||Center for Medical Image Science and Visualization (CMIV)||Linkoping University||GE Healthcare||Swedish Heart-Lung Foundation||Swedish Research Council| 12661 |

    Available from: 2012-03-08 Created: 2012-03-08 Last updated: 2017-12-07Bibliographically approved
    2. Pedometer-determined physical activity is linked to low systemic inflammation and low arterial stiffness in Type 2 diabetes
    Open this publication in new window or tab >>Pedometer-determined physical activity is linked to low systemic inflammation and low arterial stiffness in Type 2 diabetes
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    2012 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 9, p. 1119-1125Article in journal (Refereed) Published
    Abstract [en]

    Diabet. Med. 29, 11191125 (2012) Abstract Aims The aim of this study was to explore the association between pedometer-determined physical activity versus measures of obesity, inflammatory markers and arterial stiffness in people with Type 2 diabetes. Methods We analysed data from 224 men and 103 women with Type 2 diabetes, aged 5466 years. Physical activity was measured with waist-mounted pedometers during three consecutive days and the number of steps/day were calculated and classified in four groups: andlt; 5000 steps/day, 50007499 steps/day, 75009999 steps/day and andgt;= 10000 steps/day. Blood samples were analysed for lipids, HbA1c, inflammatory markers including C-reactive protein and interleukin-6. Nurses measured blood pressure and anthropometrics. Aortic pulse wave velocity was measured with applanation tonometry over the carotid and femoral arteries. Results Mean steps/day was 7683 +/- 3883 (median 7222, interquartile range 486910 343). There were no differences in age, diabetes duration, blood pressure, lipids or glycaemic control between the four groups of pedometer-determined physical activity. Subjects with higher steps/day had lower BMI (28.8 vs. 31.5 kg/m2, P andlt; 0.001), waist circumference (101.7 vs. 108.0 cm, P andlt; 0.001), lower levels of C-reactive protein (1.6 vs. 2.6 mg/l, P = 0.007), lower levels of interleukin-6 (1.9 vs. 3.8 pg ml, P andlt; 0.001) and lower pulse wave velocity (10.2 vs. 11.0 m/s, P = 0.009) compared with less physically active people. Conclusions We conclude that physical activity measured with pedometer was associated not only with less abdominal obesity, but also with decreased systemic low-grade inflammation as well as with low arterial stiffness, in people with Type 2 diabetes.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2012
    Keywords
    arterial stiffness, exercise, inflammation, obesity, pedometer, Type 2 diabetes
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-81816 (URN)10.1111/j.1464-5491.2012.03621.x (DOI)000307470200021 ()
    Note

    Funding Agencies|Medical Research Council of Southeast Sweden||Center for Medical Image Science and Visualization (CMIV), Linkoping University||GE Healthcare||Swedish Heart-Lung Foundation||Swedish Research Council|12661|

    Available from: 2012-09-26 Created: 2012-09-24 Last updated: 2017-12-07Bibliographically approved
    3. Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years
    Open this publication in new window or tab >>Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years
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    2016 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, no 7, p. 992-997Article in journal (Refereed) Published
    Abstract [en]

    Aim To explore prospectively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes.

    Methods We analysed data from 135 men and 53 women with Type 2 diabetes, aged 54–66 years. Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups: <5000 steps/day, 5000–7499 steps/day, 7500–9999 steps/day and ≥10 000 steps/day. Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years.

    Results The mean (±sd; range) number of steps/day was 8022 (±3765; 956–20 921). The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest. When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex, age, diabetes duration, HbA1c, BMI, systolic blood pressure, pulse wave velocity at baseline, β-blocker use, statin use, unemployment, smoking and diabetes medication, the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity (P=0.005). Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s.

    Conclusions We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2016
    National Category
    Endocrinology and Diabetes General Practice Geriatrics Sport and Fitness Sciences Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-125910 (URN)10.1111/dme.12873 (DOI)000379930900018 ()26227869 (PubMedID)
    Note

    Funding agencies: Medical Research Council of Southeast Sweden; Centre for Medical Image Science and Visualization (CMIV), Linkoping University; GE Healthcare; Swedish Heart-Lung Foundation; Swedish Research Council [12661]; King Gustaf V and Queen Victoria Freemason Found

    Available from: 2016-03-08 Created: 2016-03-08 Last updated: 2018-01-10Bibliographically approved
    4. A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D-3 and parathyroid hormone levels in patients with type 2 diabetes
    Open this publication in new window or tab >>A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D-3 and parathyroid hormone levels in patients with type 2 diabetes
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    2015 (English)In: Diabetology and Metabolic Syndrome, ISSN 1758-5996, E-ISSN 1758-5996, Vol. 7, no 53Article in journal (Refereed) Published
    Abstract [en]

    Background: Low levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D-3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes. Methods: The main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the "Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care" study. Patients were 55-66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry. Results: Levels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p greater than 0.9). Conclusions: Serum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV.

    Place, publisher, year, edition, pages
    BioMed Central, 2015
    Keywords
    Arteriosclerosis; Calcium; Mortality; Parathyroid hormone; Type 2 diabetes; Vitamin D
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:liu:diva-120044 (URN)10.1186/s13098-015-0049-9 (DOI)000356219100001 ()26078787 (PubMedID)
    Note

    Funding Agencies|Medical Research Council of Southeast Sweden; Futurum; King Gustaf V and Queen Victoria Freemason Foundation; GE Healthcare; Swedish Heart-Lung Foundation; Swedish Research Council [12661]; County Council of Ostergotland; Linkoping University, Department of Medical and Health Sciences

    Available from: 2015-07-06 Created: 2015-07-06 Last updated: 2017-12-04
  • 23.
    Forsander, Gun
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Bogelund, Mette
    Incentive, Denmark.
    Haas, Josephine
    Karolinska Institute, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Adolescent life with diabetes-Gender matters for level of distress. Experiences from the national TODS study2017In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 18, no 7, p. 651-659Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the relationship between diabetes distress and gender, and the association with glycemic control, social support, health behaviors, and socio-economic status. Methods: All adolescents, aged 15 to 18 years, in the national, pediatric diabetes registry SWE-DIABKIDS with type 1 diabetes were invited to complete an online questionnaire. A total of 2112 teenagers were identified. Results: 453 complete responses were valid for analyses. Young women scored significantly higher on the distress-screening instrument DDS-2. Almost half of the female respondents exhibited moderate to severe diabetes distress-more than twice the proportion than among male respondents (44% vs 19%). Females reported twice as high scores on the fear of hypoglycemia scale (P amp;lt; 0.0001) and had a higher HbA1c value than males (P amp;lt; 0.0001). Gender was highly correlated with distress level even when controlling for multiple factors that may affect distress (parameter(female) = 0.4, P = 0.0003). Particular social problems were highly significant, that is, those who trust that their parents can handle their diabetes when necessary were significantly less distressed than others (P = 0.018). Higher HbA1c levels were associated with higher distress scores (P = 0.0005 [female], P = 0.0487 [male]). Conclusions: Diabetes-related distress is a great burden for adolescents living with diabetes. Actively involved family and friends may reduce diabetes distress, but female adolescents appear to be particularly vulnerable and may need extra focus and support. Our findings indicate that pediatric diabetes teams working with teenagers must intensify the care during this vulnerable period of life in order to reduce the risk of both psychological and vascular complications in young adults.

  • 24.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology .
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology .
    Östgren, Carl Johan
    Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, West County Primary Health Care.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Microcirculatory changes in type 2 diabetes assessed with velocity resolved quantitative laser Doppler flowmetryManuscript (preprint) (Other academic)
    Abstract [en]

    The response to local heating (44oC for 20 min) was evaluated in 28 type 2 diabetes patients (DM) and 29 non-diabetes controls (ND). Microcirculatory perfusion was assessed using conventional and quantitative Laser Doppler flowmetry (cLDF and qLDF), respectively. The qLDF estimates perfusion in a physiological relevant unit (g RBC / 100 g tissue × mm/s) in a fixed output volume, separated into three velocity regions, v < 1 mm/s, 1 - 10 mm/s, and v > 10 mm/s. Perfusion in cLDF is given in arbitrary units with unknown velocity distribution and measurement volume.

    A significantly lower response in DM than in ND was found after heat provocation both for the initial peak and the plateau response, while no significant differences were found at baseline. The qLDF showed increased perfusion for the velocity regions 1-10 mm/s and above 10 mm/s, while no significant increase was found for v < 1 mm/s. In conclusion, we found a lowered LDF response to local heating in DM. The new qLDF method showed that the increased blood flow occurs in vessels with a velocity above 1 mm/s. Baseline qLDF-data indicated that a redistribution of flow to higher velocity regions was associated with longer DM duration and for DM a negative correlation between perfusion and BMI.

  • 25.
    Friederich, Malou
    et al.
    Uppsala universitet, Integrativ Fysiologi.
    Hansell, Peter
    Uppsala universitet, Integrativ Fysiologi.
    Palm, Fredrik
    Uppsala universitet, Integrativ Fysiologi.
    Diabetes, oxidative stress, nitric oxide and mitochondria function2009In: Current diabetes reviews, ISSN 1875-6417, Vol. 5, no 2, p. 120-144Article in journal (Refereed)
    Abstract [en]

    The role of altered mitochondria function has recently emerged as an important mechanism for the development of diabetic complications. Altered mitochondria function has also been implicated in the ageing process, defective insulin secretion, hypertension, arteriosclerosis, ischemia-reperfusion injury and apoptosis. Normally, the mitochondria are associated with ATP production using primarily pyruvate as the substrate, but recent reports indicate that tissue specific preferences exist. Also, the mitochondria are a substantial source of superoxide production, preferentially during states of elevated intracellular glucose concentrations. The mitochondria function is regulated by several factors including nitric oxide, oxidative stress, mammalian target of rapamycin, ADP and P(i) availability, which result in a complex regulation of ATP production and oxygen consumption, but also superoxide generation. These factors seem to be tissue specific, which warrants a more diverse mechanistic model applying to that specific tissue or cell type. This review presents the basic functions of the mitochondria and focuses on the complex interplay between oxidative stress, nitric oxide and uncoupling proteins in regulating mitochondria function with special focus on diabetes-induced alterations occurring on the mitochondria level.

  • 26.
    Fryk, Emanuel
    et al.
    University of Gothenburg, Sweden.
    Perman Sundelin, Jeanna
    University of Gothenburg, Sweden.
    Strindberg, Lena
    University of Gothenburg, Gothenburg, Sweden.
    Pereira, Maria J.
    Uppsala University, Sweden.
    Federici, Massimo
    University of Roma Tor Vergata, Italy.
    Marx, Nikolaus
    University Hospital RWTH Aachen, Germany.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Schmelz, Martin
    Heidelberg University, Germany.
    Svensson, Per-Arne
    University of Gothenburg, Sweden.
    Eriksson, Jan W.
    Uppsala University, Sweden.
    Boren, Jan
    University of Gothenburg, Sweden.
    Jansson, Per-Anders
    University of Gothenburg, Sweden.
    Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients2016In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 65, no 7, p. 998-1006Article in journal (Refereed)
    Abstract [en]

    Objective. To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. Methods. Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16 weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4 weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. Results. Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p amp;lt; 0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p amp;lt; 0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p amp;lt; 0.05) and increased by overfeeding (p amp;lt; 0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p amp;lt; 0.05) but this was independent of the insulin signal. Conclusion. Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.

  • 27.
    Gimm, Oliver
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Juhlin, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Morales, Olallo
    Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Dual-Energy Computed Tomography Localizes Ectopic Parathyroid Adenoma2010In: The Journal of Clinical Endocrinology & Metabolism, ISSN 0021-972X, Vol. 95, no 7, p. 3092-3093Article in journal (Refereed)
    Abstract [en]

    Dual-energy computed tomography (DECT) can acquire two datasets showing different attenuation levels allowing collectionof additional information about the elementary chemical compositionof the scanned material. Color can then be assigned accordingto the 80- and 140-kV computed tomography (CT) values to obtaina color-mapped, dual-energy image. DECT has been used extensivelyin our department in postmortem CT with excellent results (1).One of the advantages of DECT is that iodine contrast uptakein soft tissue can be quantified. We were wondering about itsability to localize parathyroid adenomas (PAs).

  • 28.
    Granfors, Maria
    et al.
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Augustin, Hanna
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Brekke, Hilda K
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    No association between use of multivitamin supplement containing vitamin D during pregnancy and risk of Type 1 Diabetes in the child2016In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 17, no 7, p. 525-530Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Sweden has the second highest incidence of type 1 diabetes in the world. Nutritional aspects in utero and in infancy affect the development. We conducted a survey to determine whether reported maternal use of vitamin D-containing micronutrient supplements during pregnancy was associated with the risk of developing type 1 diabetes in the child.

    METHODS:

    This report was based on data from the ABIS (All Babies In Southeast Sweden) study, with questionnaire data on 16 339 mother and infant pairs at birth and at 1-yr of age (n = 10 879), of whom 108 children were registered with type 1 diabetes before 14-16 yr of age. The questions 'during pregnancy, did you take any vitamin/mineral supplements?' and 'if yes, which? (open answer)' in addition to other lifestyle questions were answered. Logistic regression was performed with onset of type 1 diabetes as the dependent variable and vitamin D supplementation use as the independent variable, adjusted for relevant factors.

    RESULTS:

    Vitamin D supplementation during pregnancy was consumed by 9.3% of mothers whose children later got type1 diabetes and among 11.3% of those mothers whose children did not get type 1 diabetes (p = 0.532). No significant association was found between reported supplement intake of vitamin D during pregnancy and risk of type 1 diabetes, even when adjusting for factors which could influence the association.

    CONCLUSION:

    Maternal use of vitamin D-containing multivitamin supplements during pregnancy was not related to the risk of developing type 1 diabetes in children before 14-16 yr of age in Southeast of Sweden.

  • 29.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Trials of Diets for Treatment of Diabetes: A comparison of diets for treatment of type 2 diabetes, aspects on long and short term effects2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    Type 2 diabetes is a common disease and the prevalence has increased in large parts of the world. In treatment of diabetes the type of diet is of great importance considering metabolic factors such as glucose level and blood lipids. Which diet that is most beneficial to avoid diabetic complications has been heavily debated in recent decades. This thesis is based on two clinical studies designed to compare the effects of different macronutrients.

    Methods

    A clinical trial was designed to compare a low-carbohydrate diet (LCD) to a low-fat diet (LFD) in treatment of patients with type 2 diabetes. Sixty-one patients at two health care centres were included and randomized to get advice to eat a LCD or a LFD. The LCD had an energy content where 50 energy percent (E%) where from fat, 20 E% from carbohydrates and 30 E% from protein. For the LFD the nutrient composition was similar to what is traditionally recommended for treatment of type 2 diabetes in Sweden. Metabolic factors, anthropometrics and questionnaires were analysed.

    To study postprandial effects a trial was designed to compare three different diets. Twentyone patients with type 2 diabetes were included to in randomized order test the three types of diets on separate test days. On each test day the patients were served breakfast and lunch and blood samples were taken at six times these days. Glucose, lipids and hormones were analysed.

    Results

    There were equal weight reduction in the two groups in the first trial during the two-year study period. At six month when compliance was good according to diet-records, the glucose level (HbA1c) was lowered and the HDL-cholesterol was increased in the LCD group. The inflammatory markers IL-6 and IL-1Ra were significantly lower in the LCD group than in the LFD group. At 12 months the physical function, bodily pain and general health  scores improved within the LCD group only.

    In the second trial the postprandial glucose and insulin levels were lower on the LCD compared to the LFD. However, the LCD resulted in a tendency to higher postprandial triglyceride levels. The Mediterranean type of diet with all energy intake at lunch resulted in a more pronounced insulin response and a glucose level at lunch similar to that of the low-fat diet. The increase-ratio of insulin correlated to the elevation of the incretin glucose-dependent insulinotropic peptide (GIP).

    Conclusions

    In the two-year study we found benefits for the LCD group regarding glucose control and insulin doses. Furthermore, only the LCD was found to improve the subclinical inflammatory state and there were some aspects of improved well-being in this group. Aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk factors  compared with the traditional LFD and this approach could constitute a treatment alternative.

    In the postprandial state, the LCD induced lower insulin and glucose excursions than the LFD but at the same time a tendency of higher triglycerides. The long-term significance needs to be further examined. The accumulation of caloric intake from breakfast to lunch to a single large Mediterranean-style lunch-meal in type 2 diabetes might be advantageous from a metabolic perspective.

    List of papers
    1. In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss
    Open this publication in new window or tab >>In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss
    Show others...
    2012 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 8, p. 2118-2127Article in journal (Refereed) Published
    Abstract [en]

    AIMS/HYPOTHESIS: The study aimed to compare the effects of a 2 year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD), based on four group meetings to achieve compliance. METHODS: This was a prospective randomised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and randomised by drawing ballots. Patients that did not speak Swedish could not be recruited. The primary outcomes in this non-blinded study were weight and HbA(1c). Patients on the LFD aimed for 55-60 energy per cent (E%) and those on LCD for 20 E% from carbohydrate. RESULTS: The mean BMI and HbA(1c) of the participants were 32.7 ± 5.4 kg/m(2) and 57.0 ± 9.2 mmol/mol, respectively. No patients were lost to follow-up. Weight loss did not differ between groups and was maximal at 6 months: LFD -3.99 ± 4.1 kg (n = 31); LCD -4.31 ± 3.6 kg (n = 30); p < 0.001 within groups. At 24 months, patients on the LFD had lost -2.97 ± 4.9 kg and those on LCD -2.34 ± 5.1 kg compared with baseline (p = 0.002 and p = 0.020 within groups, respectively). HbA(1c) fell in the LCD group only (LCD at 6 months -4.8 ± 8.3 mmol/mol, p = 0.004, at 12 months -2.2 ± 7.7 mmol/mol, p = 0.12; LFD at 6 months -0.9 ± 8.8 mmol/mol, p = 0.56). At 6 months, HDL-cholesterol had increased with the LCD (from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l, p = 0.018) while LDL-cholesterol did not differ between groups. Insulin doses were reduced in the LCD group (0 months, LCD 42 ± 65 E, LFD 39 ± 51 E; 6 months, LCD 30 ± 47 E, LFD 38 ± 48 E; p = 0.046 for between-group change). CONCLUSIONS/INTERPRETATION: Weight changes did not differ between the diet groups, while insulin doses were reduced significantly more with the LCD at 6 months, when compliance was good. Thus, aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative. TRIAL REGISTRATION: ClinicalTrials.gov NCT01005498 FUNDING: University Hospital of Linköping Research Funds, Linköping University, the County Council of Östergötland, and the Diabetes Research Centre of Linköping University.

    Place, publisher, year, edition, pages
    Springer, 2012
    Keywords
    Blood glucose – Dietary intervention – HDL-cholesterol – LDL-cholesterol – Low-carbohydrate diet – Type 2 diabetes
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-78537 (URN)10.1007/s00125-012-2567-4 (DOI)000306122600006 ()22562179 (PubMedID)
    Available from: 2012-06-14 Created: 2012-06-14 Last updated: 2017-12-07Bibliographically approved
    2. Advice to follow a low-carbohydrate diet has a favourable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet
    Open this publication in new window or tab >>Advice to follow a low-carbohydrate diet has a favourable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet
    2014 (English)In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 46, no 3, p. 182-187Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Inflammation may play an important role in type 2 diabetes. It has been proposed that dietary strategies can modulate inflammatory activity.

    METHODS: We investigated the effects of diet on inflammation in type 2 diabetes by comparing a traditional low-fat diet (LFD) with a low-carbohydrate diet (LCD). Patients with type 2 diabetes were randomized to follow either LFD aiming for 55-60 energy per cent (E%) from carbohydrates (n = 30) or LCD aiming for 20 E% from carbohydrates (n = 29). Plasma was collected at baseline and after 6 months. C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra), IL-6, tumour necrosis factor receptor (TNFR) 1 and TNFR2 were determined.

    RESULTS: Both LFD and LCD led to similar reductions in body weight, while beneficial effects on glycaemic control were observed in the LCD group only. After 6 months, the levels of IL-1Ra and IL-6 were significantly lower in the LCD group than in the LFD group, 978 (664-1385) versus 1216 (974-1822) pg/mL and 2.15 (1.65-4.27) versus 3.39 (2.25-4.79) pg/mL, both P < 0.05.

    CONCLUSIONS: To conclude, advice to follow LCD or LFD had similar effects on weight reduction while effects on inflammation differed. Only LCD was found significantly to improve the subclinical inflammatory state in type 2 diabetes.

    Place, publisher, year, edition, pages
    Informa Healthcare, 2014
    National Category
    General Practice
    Identifiers
    urn:nbn:se:liu:diva-107718 (URN)10.3109/07853890.2014.894286 (DOI)000335584000011 ()24779961 (PubMedID)
    Available from: 2014-06-19 Created: 2014-06-19 Last updated: 2018-01-11Bibliographically approved
    3. Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus
    Open this publication in new window or tab >>Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus
    Show others...
    2014 (English)In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 106, no 2, p. 221-227Article in journal (Refereed) Published
    Abstract [en]

    Aims

    To compare the effects on health-related quality of life (HRQoL) of a 2-year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD) based on four group-meetings to achieve compliance. To describe different aspects of taking part in the intervention following the LFD or LCD.

    Methods

    Prospective, randomized trial of 61 adults with Type 2 diabetes mellitus. The SF-36 questionnaire was used at baseline, 6, 12 and 24 months. Patients on LFD aimed for 55–60 energy percent (E%) and those on LCD for 20 E% from carbohydrates. The patients were interviewed about their experiences of the intervention.

    Results

    Mean body-mass-index was 32.7 ± 5.4 kg/m2 at baseline. Weight-loss did not differ between groups and was maximal at 6 months, LFD: −3.99 ± 4.1 kg, LCD: −4.31 ± 3.6 kg (p < 0.001 within groups). There was an increase in the physical component score of SF-36 from 44.1 (10.0) to 46.7 (10.5) at 12 months in the LCD group (p < 0.009) while no change occurred in the LFD group (p < 0.03 between groups). At 12 months the physical function, bodily pain and general health scores improved within the LCD group (p values 0.042–0.009) while there was no change within the LFD group.

    Conclusions

    Weight-changes did not differ between the diet groups while improvements in HRQoL only occurred after one year during treatment with LCD. No changes of HRQoL occurred in the LFD group in spite of a similar reduction in body weight.

     

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Type 2 diabetes mellitus; Dietary intervention; Low-carbohydrate diet; SF-36
    National Category
    Clinical Medicine Basic Medicine
    Identifiers
    urn:nbn:se:liu:diva-112690 (URN)10.1016/j.diabres.2014.08.032 (DOI)000346060500019 ()25271116 (PubMedID)
    Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2018-01-11Bibliographically approved
    4. A Randomized Cross-Over Trial of the Postprandial Effects of Three Different Diets in Patients with Type 2 Diabetes
    Open this publication in new window or tab >>A Randomized Cross-Over Trial of the Postprandial Effects of Three Different Diets in Patients with Type 2 Diabetes
    Show others...
    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, p. e79324-Article in journal (Refereed) Published
    Abstract [en]

    Background: In the clinic setting both fasting levels of glucose and the area under the curve (AUC) of glucose, by determination of HbA1c levels, are used for risk assessments, in type 2 diabetes (NIDDM). However little is known about postprandial levels, and hence AUC, regarding other traditional risk factors such as insulin and blood-lipids and how this is affected by different diets. less thanbrgreater than less thanbrgreater thanObjective: To study postprandial effects of three diets, during a single day, in NIDDM. less thanbrgreater than less thanbrgreater thanMethods: A low-fat diet (45-56 energy-% from carbohydrates), and a low-carbohydrate diet (16-24 energy-% from carbohydrates) was compared with a Mediterranean-style diet (black coffee for breakfast and the same total-caloric intake as the other two diets for lunch with red wine, 32-35 energy-% from carbohydrates) in a randomized cross-over design. Total-caloric intake/test-day at the clinic from food was 1025-1080 kCal in men and 905-984 kCal in women. The test meals were consumed at a diabetes ward under supervision. less thanbrgreater than less thanbrgreater thanResults: Twenty-one participants were recruited and 19 completed the studies. The low-carbohydrate diet induced lower insulin and glucose excursions compared with the low-fat diet (pandlt;0.0005 for both AUC). The insulin-response following the single Mediterranean-style lunch-meal was more pronounced than during the low-fat diet lunch (insulin increase-ratio of the low-fat diet: 4.35 +/- 2.2, of Mediterranean-style diet: 8.12 +/- 5.2, p=0.001) while postprandial glucose levels were similar. The increase-ratio of insulin correlated with the elevation of the incretin glucose-dependent insulinotropic-polypeptide following the Mediterranean-style diet lunch (Spearman, r = 0.64, p = 0.003). less thanbrgreater than less thanbrgreater thanConclusions: The large Mediterranean-style lunch-meal induced similar postprandial glucose-elevations as the low-fat meal despite almost double amount of calories due to a pronounced insulin-increase. This suggests that accumulation of caloric intake from breakfast and lunch to a single large Mediterranean style lunch-meal in NIDDM might be advantageous from a metabolic perspective.

    Place, publisher, year, edition, pages
    Public Library of Science, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-102850 (URN)10.1371/journal.pone.0079324 (DOI)000327652100009 ()
    Available from: 2014-01-07 Created: 2014-01-02 Last updated: 2017-12-06
  • 30.
    Gutefeldt, Kerstin
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Hedman, Christina A
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Thyberg, Ingrid S M
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Bachrach-Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Upper extremity impairments in type 1 diabetes with long duration: common problems with great impact on daily life2017In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, p. 1-8Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To investigate the prevalence, activity limitations and potential risk factors of upper extremity impairments in type 1 diabetes in comparison to controls.

    METHODS: In a cross-sectional population-based study in the southeast of Sweden, patients with type 1 diabetes <35 years at onset, duration ≥20 years, <67 years old and matched controls were invited to answer a questionnaire on upper extremity impairments and activity limitations and to take blood samples.

    RESULTS: Seven hundred and seventy-three patients (ages 50 ± 10 years, diabetes duration 35 ± 10 years) and 708 controls (ages 54 ± 9 years) were included. Shoulder pain and stiffness, hand paraesthesia and finger impairments were common in patients with a prevalence of 28-48%, which was 2-4-folds higher than in controls. Compared to controls, the patients had more bilateral impairments, often had coexistence of several upper extremity impairments, and in the presence of impairments, reported more pronounced activity limitations. Female gender (1.72 (1.066-2.272), p = 0.014), longer duration (1.046 (1.015-1.077), p = 0.003), higher body mass index (1.08 (1.017-1.147), p = 0.013) and HbA1c (1.029 (1.008-1.05), p = 0.007) were associated with upper extremity impairments.

    CONCLUSIONS: Compared to controls, patients with type 1 diabetes have a high prevalence of upper extremity impairments, often bilateral, which are strongly associated with activity limitations. Recognising these in clinical practise is crucial, and improved preventative, therapeutic and rehabilitative interventions are needed. Implications for rehabilitation Upper extremity impairments affecting the shoulder, hand and fingers are common in patients with type 1 diabetes, the prevalence being 2-4-fold higher compared to non-diabetic persons. Patients with diabetes type 1 with upper extremity impairments have more pronounced limitations in daily activities compared to controls with similar impairments. Recognising upper extremity impairments and activity limitations are important and improved preventive, therapeutic and rehabilitation methods are needed.

    The full text will be freely available from 2018-11-05 13:21
  • 31.
    Haarhaus, Mathias
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. Karolinska Institute, Sweden.
    Brandenburg, Vincent
    RWTH University Hospital Aachen, Germany.
    Kalantar-Zadeh, Kamyar
    University of Calif Irvine, CA 92868 USA; University of Calif Los Angeles, CA 90502 USA.
    Stenvinkel, Peter
    Karolinska Institute, Sweden.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD2017In: Nature Reviews Nephrology, ISSN 1759-5061, E-ISSN 1759-507X, Vol. 13, no 7, p. 429-442Article, review/survey (Refereed)
    Abstract [en]

    Cardiovascular disease is the main cause of early death in the settings of chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), and ageing. Cardiovascular events can be caused by an imbalance between promoters and inhibitors of mineralization, which leads to vascular calcification. This process is akin to skeletal mineralization, which is carefully regulated and in which isozymes of alkaline phosphatase (ALP) have a crucial role. Four genes encode ALP isozymes in humans. Intestinal, placental and germ cell ALPs are tissue-specific, whereas the tissue-nonspecific isozyme of ALP (TNALP) is present in several tissues, including bone, liver and kidney. TNALP has a pivotal role in bone calcification. Experimental overexpression of TNALP in the vasculature is sufficient to induce vascular calcification, cardiac hypertrophy and premature death, mimicking the cardiovascular phenotype often found in CKD and T2DM. Intestinal ALP contributes to the gut mucosal defence and intestinal and liver ALPs might contribute to the acute inflammatory response to endogenous or pathogenic stimuli. Here we review novel mechanisms that link ALP to vascular calcification, inflammation, and endothelial dysfunction in kidney and cardiovascular diseases. We also discuss new drugs that target ALP, which have the potential to improve cardiovascular outcomes without inhibiting skeletal mineralization.

  • 32.
    Halling Linder, Cecilia
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Magnusson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Glycation Contributes to Interaction Between Human Bone Alkaline Phosphatase and Collagen Type I2016In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 98, no 3, p. 284-293Article in journal (Refereed)
    Abstract [en]

    Bone is a biological composite material comprised primarily of collagen type I and mineral crystals of calcium and phosphate in the form of hydroxyapatite (HA), which together provide its mechanical properties. Bone alkaline phosphatase (ALP), produced by osteoblasts, plays a pivotal role in the mineralization process. Affinity contacts between collagen, mainly type II, and the crown domain of various ALP isozymes were reported in a few in vitro studies in the 1980s and 1990s, but have not attracted much attention since, although such interactions may have important implications for the bone mineralization process. The objective of this study was to investigate the binding properties of human collagen type I to human bone ALP, including the two bone ALP isoforms B1 and B2. ALP from human liver, human placenta and E. coli were also studied. A surface plasmon resonance-based analysis, supported by electrophoresis and blotting, showed that bone ALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. Further, the B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform. Human bone and liver ALP (with identical amino acid composition) displayed pronounced differences in binding, revealing that post-translational glycosylation properties govern these interactions to a large extent. In conclusion, this study presents the first evidence that glycosylation differences in human ALPs are of crucial importance for protein–protein interactions with collagen type I, although the presence of the ALP crown domain may also be necessary. Different binding affinities among the bone ALP isoforms may influence the mineral-collagen interface, mineralization kinetics, and degree of bone matrix mineralization, which are important factors determining the material properties of bone.

  • 33.
    Hanberger, Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Inst Diabet Res, Germany.
    Froehlich-Reiterer, Elke
    Med Univ Graz, Austria.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden; Jonkoping Univ, Sweden.
    Hofer, Sabine
    Med Univ Innsbruck, Austria.
    Type 1 diabetes during adolescence: International comparison between Germany, Austria, and Sweden2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 3, p. 506-511Article in journal (Refereed)
    Abstract [en]

    Objectives: By using pediatric diabetes quality registries in Austria, Germany, and Sweden treatment of type 1 diabetes and the outcome of care during the vulnerable adolescence period were compared. Methods: Data in DPV, broadly used in Austria and Germany, and Swediabkids used in Sweden, from clinical visits in the year 2013 on 14 383 patients aged 11 to 16 years regarding hemoglobin A1c (HbA1c), insulin regimen, body mass index (BMI)-SD score (SDS), blood pressure, hypoglycemia, ketoacidosis, and smoking habits were analyzed. Results: Patients in Sweden had fewer clinical visits per year (P amp;lt; .05), lower insulin dose per kg (P amp;lt; .001), and lower proportion of fast acting insulin compared with Germany and Austria (P amp;lt; .001). The proportion of pump users was higher in Sweden (P amp;lt; .001). Patients in Sweden had lower mean HbA1c levels (Austria: 64 mmol/mol, Germany: 63 mmol/mol, and Sweden: 61 mmol/mol [8.0%, 7.9%, and 7.7%, respectively]; P amp;lt; .001). The frequency of severe hypoglycemia was higher in Sweden while it was lower for ketoacidosis (3.3% and 1.1%, respectively) than in Austria (1.1% and 5.3%) and Germany (2.0% and 4.4%) (P amp;lt; .001). Girls in all 3 countries had higher HbA1c and BMI-SDS than boys. Conclusions: Sharing data between diabetes registries and nations enables us to better understand differences in diabetes outcome between countries. In this particular comparison, pediatric patients with diabetes in Sweden were more often treated with insulin pump, had lower HbA1c levels and a higher rate of severe hypoglycemia. Patients in Austria and Germany used rapid acting insulin analogs more often and had a lower rate of ketoacidosis.

  • 34.
    Hedbrant, Johan
    Linköping University, Department of Management and Engineering, Applied Thermodynamics and Fluid Mechanics. Linköping University, Faculty of Science & Engineering.
    Kostråd till diabetiker baseras inte på studier av diabetiker!: en kritik av ovetenskapen inom vetenskapen2006In: 2000-Talets Vetenskap, ISSN 1654-7810, no 2, p. 14-15Article in journal (Other academic)
    Abstract [sv]

    Övervikten i Sverige började öka sedan nyckelhålsmärkningen infördes 1989. I USA som ligger före Sverige vad gäller övervikt ökar nu typ-2-diabetes. Som intresserad lekman undrar man förstås varför, och det är glädjande att även näringsexperter börjar intressera sig för tänkbara orsaker. Johan Hedbrant har studerat det vetenskapliga underlaget för kostråden och funnit häpnadsväckande brister.

    I två artiklar i Läkartidningen hänvisar Larsson, Rothenberg och Vessby till nyligen uppdaterade kostråd av Diabetes Nutrition Study Group (DNSG), och noterar en skillnad jämfört med en typ av dieter som visat sig ge stora fördelar vid övervikt och typ-2-diabetes. De senare bygger på en reduktion av kolhydratinnehållet, medan DNSG ekommenderar upp till 60 energiprocent kolhydrat. I skenet av råden att äta mer kolhydrat och tredubblingen av typ-2-diabetes, undrar man lite över vetenskapen bakom att rekommendera mer av det näringsämne typ-2-diabetiker inte tål.

  • 35.
    Hedbrant, Johan
    et al.
    Department of Pediatrics, Faculty of Health Sciences, Faculty of Health Sciences, Linköping, Sweden.
    Ludvigsson, Johnny
    Department of Pediatrics, Faculty of Health Sciences, Faculty of Health Sciences, Linköping, Sweden.
    Use of computer simulator training in the education of diabetic teenagers1995In: Practical Diabetes International, ISSN 1357-8170, E-ISSN 1528-252X, Vol. 12, no 1, p. 18-21Article in journal (Refereed)
    Abstract [en]

    Diabetic patients learning to manage diabetes are often at the mercy of trial and error. To speed up and improve the learning process a computerised diabetes simulator may be used for experiments with food, insulin and exercise without risk of inconvenience.

    When measuring the impact of computer training, only 11 out of 58 diabetic teenagers wanted to participate in the study. These diabetic teen- agers were educated in four computer lessons and evaluated with respect to metabolic control, emotional adjustment, locus of control, self-esteem and ability to discuss treatment problems. It was not possible to recruit a control group.

    In a few individuals there were significant improvements in locus-of- control, self-esteem, knowledge and diabetes related stress. Side-effects were an increased level of guilt and an alienation from medical pro- fessionals.

    The computer training was considered to be enjoyable and of great value. Consistent with our hope, the participants regarded the computer simulator as a source of inspiration rather than as an instrument for calculating the optimal insulin regimen.

    We conclude that although young people get more and more used to computers, still only a minority are attracted by this type of education. On a group basis limited computer training has no significant influence, but for certain individuals computer simulation may be a good educational tool.

  • 36.
    Hedbrant, Johan
    et al.
    Center of Technology Transfer, Linköpping Institure of Technology, Linköping, Sweden.
    Ludvigsson, Johnny
    Department of Pediatrics, Faculty of Health Sciences, Linköping, Sweden.
    Nordenskjöld, Kerstin
    Department of Pediatrics, Faculty of Health Sciences, Linköping, Sweden.
    Särimner: a computer model of diabetes physiology for education of physicians and patients.1991In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 14, no 2, p. 113-122Article in journal (Refereed)
    Abstract [en]

    Often diabetic patients have developed their skills by some trial-and-error-like training over a long period of time. To minimize this inconvenience we have made a mathematical model to facilitate diabetes education. The model consists of a number of blocks involved in diabetes physiology: digestion, blood (transport), pancreas, injected insulin absorption, liver, muscles, kidneys, metabolism and insulin sensitivity. The model serves as a demonstration object and the user can change meals, exercise and injections and see the resulting blood glucose level. A more experienced user can search for further explanations of different phenomena deeper in the physiology of the model. The model does not solve any problem for the user, but creates a learning situation in which the user, led by his own curiosity, successively increases his experience of diabetes physiology. Särimner is implemented as an easy-to-use menu driven computer program for IBM PC-clones with Hercules, EGA or VGA graphics.

  • 37.
    Hernar, Ingvild
    et al.
    Haukeland Hospital, Norway; Western Norway University of Appl Science, Norway.
    Haltbakk, Johannes
    Western Norway University of Appl Science, Norway.
    Broström, Anders
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Clinical Neurophysiology. Western Norway University of Appl Science, Norway; Jonköping University, Sweden.
    Differences in depression, treatment satisfaction and injection behaviour in adults with type 1 diabetes and different degrees of lipohypertrophy2017In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 26, no 23-24, p. 4583-4596Article in journal (Refereed)
    Abstract [en]

    Aims and objectivesTo assess the prevalence of lipohypertrophy, and to compare differences in external, personal and regimen factors in adults with type 1 diabetes and different degrees of lipohypertrophy. BackgroundSuboptimal insulin injection behaviour is associated with lipohypertrophy, which may affect insulin absorption and lead to blood glucose fluctuations. Few, if any studies have investigated how external, personal and regimen factors differ in people with type 1 diabetes and different degrees of lipohypertrophy. DesignA cross-sectional study including adults with type 1 diabetes at a diabetes outpatient clinic in a Norwegian university hospital. MethodsParticipants (n=215) were included consecutively at scheduled appointments. Sociodemographic, diabetes and insulin treatment data, and self-report questionnaires concerning patient activation (Patient Activation Measure), depression (Patient Health Questionnaire-2), diabetes distress (Diabetes Distress Scale), type D personality (14-item Type D scale), treatment satisfaction (Insulin Treatment Satisfaction Questionnaire) and motivation (Treatment Self-Regulation Questionnaire), were collected. Lipohypertrophic injection sites were identified by palpation by diabetes specialist nurses. ResultsLipohypertrophy was present in 53% and was more frequent in insulin pen users (63%) compared to insulin pump users (34%). Participants with two or more lipohypertrophic areas had higher depression scores, lower treatment satisfaction with glycaemic control, higher bolus doses and reported suboptimal injection behaviour compared to those with no lipohypertrophic areas. There were no differences in patient activation, diabetes distress, type D personality or motivation between the groups. Discussion and conclusionCompared to pump treatment, pen treatment requires greater awareness of injection technique. Symptoms of depression and lower treatment satisfaction might affect diabetes self-management and glycaemic control, but the association with lipohypertrophy needs further exploration. Relevance to clinical practiceLipohypertrophy is more frequent in insulin pen users compared to pump users. Nurses should focus on injection technique education, and should also consider screening for depressive symptoms and treatment satisfaction as these factors could be associated with development of lipohypertrophy.

  • 38.
    Ingves, Simon
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vilhelmsson, Nathalie
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A randomized cross-over study of the effects of macronutrient composition and meal frequency on GLP-1, ghrelin and energy expenditure in humans2017In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 93, p. 20-26Article in journal (Refereed)
    Abstract [en]

    Objective: Little is known about human postprandial increase of energy expenditure and satiety-associated hormones in relation to both meal frequency and macronutrient composition. Design: Randomized cross-over study with four conditions for each participant. Methods: Seven men and seven women (mean age 23 +/- 1.5 years) were randomly assigned to the order of intake of a 750 kcal drink with the same protein content while having either 20 energy-percent (E%) or 55 E% from carbohydrates and the remaining energy from fat. Participants were also randomized to consume the drinks as one large beverage or as five 150 kcal portions every 30 min, starting in the fasting state in the morning. Energy expenditure (EE) was determined every 30 min by indirect calorimetry. Hormonal responses and suppression of hunger (by visual-analogue scales) were also studied. A p amp;lt; 0.013 was considered statistically significant following Bonferroni-correction. Results: The area under the curve (AUC) for EE was higher during the 2.5 h after the high-carbohydrate drinks (p = 0.005 by Wilcoxon) and also after ingesting one drink compared with five (p = 0.004). AUC for serum active GLP-1 was higher after single drinks compared with five beverages (p = 0.002). Although GLP-1 levels remained particularly high at the end of the test during the low-carbohydrate meals, the AUC did not differ compared with the high-carbohydrate occasions (low-carbohydrate: 58.9 +/- 18 pg/ml/h, high-carbohydrate: 45.2 +/- 16 pg/ml/h, p = 0.028). Hunger sensations were suppressed more after single beverages compared with five small drinks (p = 0.009). Conclusions: We found higher EE during 2.5 h following one large drink compared with five smaller beverages. Since hunger was also suppressed more efficiently, and serum GLP-1 levels were higher after one compared with five smaller drinks, our findings do not support nibbling to avoid hunger or to keep up EE from morning to noon.

  • 39.
    Iredahl, Fredrik
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Högstedt, Alexandra
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Henricson, Joakim
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Tesselaar, Erik
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Farnebo, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Skin glucose metabolism and microvascular blood flow during local insulin delivery and after an oral glucose load2016In: Microcirculation, ISSN 1073-9688, E-ISSN 1549-8719, Vol. 23, no 7, p. 597-605Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Insulin causes capillary recruitment in muscle and adipose tissue, but the metabolic and microvascular effects of insulin in the skin have not been studied in detail. The aim of this study was to measure glucose metabolism and microvascular blood flow in the skin during local insulin delivery and after an oral glucose load.

    METHODS: Microdialysis catheters were inserted intracutanously in human subjects. In eight subjects two microdialysis catheters were inserted, one perfused with insulin and one with control solution. First the local effects of insulin was studied, followed by a systemic provocation by an oral glucose load. Additionally, as control experiment, six subjects did not recieve local delivery of insulin or the oral glucose load. During microdialysis the local blood flow was measured by urea clearance and by laser speckle contrast imaging (LSCI).

    RESULTS: Within 15 minutes of local insulin delivery, microvascular blood flow in the skin increased (urea clearance: P=.047, LSCI: P=.002) paralleled by increases in pyruvate (P=.01) and lactate (P=.04), indicating an increase in glucose uptake. An oral glucose load increased urea clearance from the catheters, indicating an increase in skin perfusion, although no perfusion changes were detected with LSCI. The concentration of glucose, pyruvate and lactate increased in the skin after the oral glucose load.

    CONCLUSION: Insulin has metabolic and vasodilatory effects in the skin both when given locally and after systemic delivery through an oral glucose load.

  • 40.
    Jennersjö, Pär
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Guldbrand, Hans
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, West County Primary Health Care.
    Björne, Stefan
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A prospective observational study of all-cause mortality in relation to serum 25-OH vitamin D-3 and parathyroid hormone levels in patients with type 2 diabetes2015In: Diabetology and Metabolic Syndrome, ISSN 1758-5996, E-ISSN 1758-5996, Vol. 7, no 53Article in journal (Refereed)
    Abstract [en]

    Background: Low levels of vitamin D have been related to increased mortality and morbidity in several non-diabetic studies. We aimed to prospectively study relationships between serum 25-OH vitamin D-3 (vitamin D) and of serum parathyroid hormone (PTH) to total mortality in type 2 diabetes. We also aimed to compare the levels of these potential risk-factors in patients with and without diabetes. Methods: The main study design was prospective and observational. We used baseline data from 472 men and 245 women who participated in the "Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care" study. Patients were 55-66 years old at recruitment, and an age-matched non-diabetic sample of 129 individuals constituted controls for the baseline data. Carotid-femoral pulse-wave velocity (PWV) was measured with applanation-tonometry and carotid intima-media thickness (IMT) with ultrasound. Patients with diabetes were followed for all-cause mortality using the national Swedish Cause of Death Registry. Results: Levels of vitamin D were lower in patients with diabetes than in controls, also after correction for age and obesity, while PTH levels did not differ. Nine women and 24 men died during 6 years of median follow up of the final cohort (n = 698). Vitamin D levels were negatively related to all-cause mortality in men independently of age, PTH, HbA1c, waist circumference, 24-h systolic ambulatory-blood pressure (ABP) and serum-apoB (p = 0.049). This finding was also statistically significant when PWV and IMT were added to the analyses (p = 0.028) and was not affected statistically when medications were also included in the regression-analysis (p = 0.01). In the women with type 2 diabetes, levels of PTH were positively related with all-cause mortality in the corresponding calculations (p = 0.016 without PWV and IMT, p = 0.006 with PWV and IMT, p = 0.045 when also adding medications to the analysis), while levels of vitamin D was without statistical significance (p greater than 0.9). Conclusions: Serum vitamin D in men and serum PTH in women give prognostic information in terms of total-mortality that are independent of regular risk factors in addition to levels of ABP, IMT and PWV.

  • 41.
    Jennersjö, Pär
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Pedometer-determined physical activity level and change in arterial stiffness in Type 2 diabetes over 4 years2016In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 33, no 7, p. 992-997Article in journal (Refereed)
    Abstract [en]

    Aim To explore prospectively the correlation between the level of pedometer-determined physical activity at the start of the study and the change in pulse wave velocity from baseline to 4 years later in people with Type 2 diabetes.

    Methods We analysed data from 135 men and 53 women with Type 2 diabetes, aged 54–66 years. Physical activity was measured with waist-mounted pedometers on 3 consecutive days and the numbers of steps/day at baseline were classified into four groups: <5000 steps/day, 5000–7499 steps/day, 7500–9999 steps/day and ≥10 000 steps/day. Pulse wave velocity was measured using applanation tonometry over the carotid and femoral arteries at baseline and after 4 years.

    Results The mean (±sd; range) number of steps/day was 8022 (±3765; 956–20 921). The participants with the lowest level of physical activity had a more pronounced increase in the change in pulse wave velocity compared with the participants with the highest. When change in pulse wave velocity was analysed as a continuous variable and adjusted for sex, age, diabetes duration, HbA1c, BMI, systolic blood pressure, pulse wave velocity at baseline, β-blocker use, statin use, unemployment, smoking and diabetes medication, the number of steps/day at baseline was significantly associated with a less steep increase in change in pulse wave velocity (P=0.005). Every 1000 extra steps at baseline corresponded to a lower increase in change in pulse wave velocity of 0.103 m/s.

    Conclusions We found that a high level of pedometer-determined physical activity was associated with a slower progression of arterial stiffness over 4 years in middle-aged people with Type 2 diabetes.

  • 42.
    Johansson, Björn
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Ophthalmology in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Opacification of anterior part of hydrophilic acrylic IOL or a prelenticular inflammatory membrane?2012In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 38, no 6, p. 1115-1116Article in journal (Refereed)
    Abstract [en]

    In their recent case report, Park and Chuck1 describe the bilateral appearance of an opacification at the plane of the anterior surface of the hydrophilic acrylic Akreos MI60 intraocular lens (IOL) (Bausch & Lomb). The patient's general history of diabetes mellitus, proliferative retinopathy, and iris rubeosis explains the limited pupil dilation preventing visualization of the capsulorhexis opening in their slitlamp images.

  • 43.
    Jonasson, Hanna
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Bergstrand, Sara
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Ödeshög.
    Bjarnegård, Niclas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Skin microvascular endothelial dysfunction is associated with type 2 diabetes independently of microalbuminuria and arterial stiffness2017In: Diabetes & Vascular Disease Research, ISSN 1479-1641, E-ISSN 1752-8984, Vol. 14, no 4, p. 363-371, article id UNSP 1479164117707706Article in journal (Refereed)
    Abstract [en]

    Skin and kidney microvascular functions may be affected independently in diabetes mellitus. We investigated skin microcirculatory function in 79 subjects with diabetes type 2, where 41 had microalbuminuria and 38 not, and in 41 age-matched controls. The oxygen saturation, fraction of red blood cells and speed-resolved microcirculatory perfusion (% red blood cells x mm/s) divided into three speed regions: 0-1, 1-10 and above 10 mm/s, were assessed during baseline and after local heating of the foot with a new device integrating diffuse reflectance spectroscopy and laser Doppler flowmetry. Arterial stiffness was assessed as carotid-femoral pulse wave velocity. Subjects with diabetes and microalbuminuria had significantly higher carotid-femoral pulse wave velocity compared to subjects without microalbuminuria and to controls. The perfusion for speeds 0-1 mm/s and red blood cell tissue fraction were reduced in subjects with diabetes at baseline and after heating, independent of microalbuminuria. These parameters were correlated to HbA1c. In conclusion, the reduced nutritive perfusion and red blood cell tissue fraction in type 2 diabetes were related to long-term glucose control but independent of microvascular changes in the kidneys and large-vessel stiffness. This may be due to different pathogenic pathways in the development of nephropathy, large-vessel stiffness and cutaneous microvascular impairment.

  • 44.
    Jonson, Carl-Oscar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences.
    The Importance of CTLA-4 and HLA Class II for Type 1 Diabetes Immunology2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 1 Diabetes (T1D) is a serious chronic disease that results from an autoimmune destruction of the insulin-producing beta cells. Sweden has the second highest incidence of T1D in the world, and it affects more and more children each year. Genes controlling key functions of the immune system regulation of autoimmunity has been associated to T1D. Polymorphism in the Human Leukocyte Antigen (HLA) Class II is a major risk determinant for T1D but also Cytotoxic T lymphocyte Antigen 4 (CTLA-4) polymorphism can affect predisposition. Immune responses towards Glutamic Acid Decarboxylase 65 (GAD65), Insulin, insulinoma-associated antigen 2 (IA-2) and Heat Shock protein 60 have all been implicated in T1D pathogenesis.

    We aimed to study the effect and role of CTLA-4 and HLA Class II in the T1D immunity. By focusing on the immune responses associated to T1D in healthy children with risk genotypes we aimed to study immunological effects of T1D risk.

    We found that HSP60-peptide induced a higher IFN- response in subjects with risk associated CTLA-4 +49GG allele while GAD65 induced IL-4 secretion was lower in risk subjects. Individuals with T1D neutral HLA showed higher IFN- responses to GAD65 than DR3-DQ2 and DR4-DQ8 positive children. We did also detect that T1D patients have reduced IFN- responses to GAD65 compared to healthy children. Interestingly, HLA and CTLA-4 risk genotype seem to reduce those responses to become similar to responses of T1D patients. We also found that CTLA-4 and HLA risk is associated to reduced percentages of lymphocytes expressing intracellular CTLA-4 in healthy children. In another study we recorded maintained levels of CTLA-4 and TGF- mRNA responsiveness to GAD65 in recent onset T1D patients receiving ECP treatment although clinical outcome was certainly limited.

    In conclusion, HLA Class II risk genes but also CTLA-4 +49A/G to some extent, influence CTLA-4 capacity and T1D protective antigen-specific responses in a manner that might explain the genes’ predisposing and pathogenic capability.

    List of papers
    1. The importance of CTLA-4 polymorphism and Human leukocyte antigen genotype for the induction of diabetes-associated cytokine response in healthy school children
    Open this publication in new window or tab >>The importance of CTLA-4 polymorphism and Human leukocyte antigen genotype for the induction of diabetes-associated cytokine response in healthy school children
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    2007 (English)In: Pediatric Diabetes, ISSN 1399-543X, Vol. 8, no 4, p. 185-192Article in journal (Refereed) Published
    Abstract [en]

    Background: Type 1 diabetes (T1D) is an autoimmune disease associated with the destruction of pancreatic β cells and genetically linked to human leukocyte antigen (HLA) class II DR3-DQ2 and DR4-DQ8 haplotypes. The +49A/G polymorphism of the immunoregulatory cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene is also associated with T1D. Genetic and environmental risk factors precede the onset of T1D, which is characterized by a T helper 1 cell-dominating cytokine response to diabetes-related autoantigens.

    Aim: To investigate immunological differences between healthy children with and without CTLA-4 +49A/G and HLA genetic susceptibility for T1D.

    Study design: Young, 7–15 years of age, healthy subjects (n = 58) were investigated to test whether CTLA-4 +49A/G genotype was associated with enzyme-linked immunospot assay T-cell responses to T1D-related autoantigens. Because T1D is primarily HLA-DQ associated, we stratified the healthy subjects by HLA genotypes associated with the disease.

    Results: Peptide of heat shock protein 60 induced a higher interferon-γ (IFN-γ) response in subjects with risk-associated CTLA-4 polymorphism (GG genotype) (p = 0.02) while glutamic acid decarboxylase 65-induced interleukin-4 (IL-4) secretion was lower in GG genotype subjects (p = 0.02).

    Conclusion: The increased IFN-γ response and lower IL-4 response toward diabetes-related autoantigens shown in CTLA-4 +49 GG risk subjects show a possible mechanism for the association between CTLA-4 and T1D.

    Keywords
    CTLA-4, cytokines, HLA, SNP, type 1 diabetes mellitus
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12876 (URN)10.1111/j.1399-5448.2007.00245.x (DOI)
    Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2009-08-19
    2. CTLA-4 Polymorfism, Type 1 Diabetes-risk Human Leukocyte Antigen-genotypes, insulin gene polymorphism and Regulatory T-cell Marker Expression in 5-year-old children
    Open this publication in new window or tab >>CTLA-4 Polymorfism, Type 1 Diabetes-risk Human Leukocyte Antigen-genotypes, insulin gene polymorphism and Regulatory T-cell Marker Expression in 5-year-old children
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    2006 (English)In: Clinical & Experimental Immunology, ISSN 0009-9104, Vol. 145, no 1, p. 48-55Article in journal (Refereed) Published
    Abstract [en]

    Regulatory T cells (Treg) are involved in the maintenance of peripheral tolerance by suppression of autoreactive lymphocytes that have avoided thymic depletion. The defective function of Treg cells has recently attracted attention in autoimmune diseases such as type 1 diabetes (T1D), rheumatoid arthritis and multiple sclerosis. Susceptibility to these diseases is associated with specific human leucocyte antigen (HLA) class II and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene polymorphisms. This study aimed to investigate the relationship between HLA class II and CTLA +49 A/G polymorphisms associated with susceptibility to T1D and the number and characteristics of Treg cells in children. Samples from 47 5-year-old children who participated in the All Babies in South-east Sweden (ABIS) follow-up study were grouped according to the presence of the T1D risk-associated HLA genotype (DQA1*0501–DQB1*0201, DQA1*0301–DQB1*0302) or neutral HLA genotypes. Lower percentages of CD4+ T cells (= 0·03) and CD4+ CD25high cells (= 0·06) expressing intracellular CTLA-4 were detected in samples from children with CTLA-4 +49GG compared to children with the +49AA genotype. Similarly, lower percentages of CD4+ (= 0·002) and CD4+ CD25high (= 0·002) cells expressing CTLA-4 were observed in children positive for HLA DQA1*0501–DQB1*0201 and DQA1*0301–DQB1*0302 (= 0·04 for CD4+ and P = 0·02 for CD4+ CD25high) risk haplotypes when compared to children without these alleles. The percentage of CD25high cells among CD4+ cells was correlated inversely with CTLA-4 mRNA expression in PBMC (r = –0·56, P = 0·03). Decreased levels of CTLA-4 in CD4+ and CD4+ CD25high cells in individuals with CTLA-4 and HLA class II alleles associated with T1D may contribute to the initiation and/or progression of autoimmune response.

    Keywords
    CTLA-4, HLA, regulatory T cells
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12877 (URN)10.1111/j.1365-2249.2006.03106.x (DOI)
    Available from: 2008-01-11 Created: 2008-01-11
    3. Regulatory T-cell associated activity in Photopheresis-induced Immune tolerance in Recent Onset Type 1 Diabetes Children
    Open this publication in new window or tab >>Regulatory T-cell associated activity in Photopheresis-induced Immune tolerance in Recent Onset Type 1 Diabetes Children
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    2008 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 153, no 2, p. 174-181Article in journal (Refereed) Published
    Abstract [en]

    Extracorporeal photochemotherapy (ECP) has demonstrated immunological effects. The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-β are associated with regulatory T cell activity. The aim of the study was to evaluate the regulatory T cell-associated effect of ECP in recent onset type 1 diabetic (T1D) children. Children (n = 20) with T1D received photopheresis 8-methoxypsoralen + ECP or placebo + shampheresis. Peripheral blood mononuclear cells (PBMC) collected pretreatment (day 1) and post-treatment (day 90) were stimulated with phytohaemagglutinin (PHA) and T1D-associated glutamic acid decarboxylase 65 (GAD65) peptide a.a. 247–279. CTLA-4, sCTLA-4, FoxP3 and TGF-β mRNA transcription was quantified. Photopheresis-treated individuals' relative mRNA expression was generally maintained during the course of the study. Placebo individuals increased in spontaneous CTLA-4 mRNA (P < 0·05) but decreased in expression after stimulation with GAD65-peptide (P < 0·05) and PHA (P < 0·05). Spontaneous TGF-β (P < 0·05) increased whereas PHA- (P < 0·01) and GAD65-peptide (P < 0·01)-induced TGF-β expression decreased in the placebo group, whereas it was maintained in the treated group. Without intervention, expression of CTLA-4 and TGF-β, stimulated with PHA and GAD65 peptide, decreased with time, with a parallel reduction of GAD65-peptide and PHA-stimulated TGF-β expression. These parameters were counteracted by ECP. In conclusion, our results indicate that ECP maintains regulatory T cell-associated activity in recent-onset T1D.

    Keywords
    children, extracorporeal photochemotherapy, T1D, Treg
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-12878 (URN)10.1111/j.1365-2249.2008.03625.x (DOI)
    Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2017-12-14
    4. Children with CTLA-4 +49A/G and HLA class II risk alleles show similar Th1-like response towards GAD65 as children with manifest type 1 diabetes
    Open this publication in new window or tab >>Children with CTLA-4 +49A/G and HLA class II risk alleles show similar Th1-like response towards GAD65 as children with manifest type 1 diabetes
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:liu:diva-12879 (URN)
    Available from: 2008-01-11 Created: 2008-01-11 Last updated: 2010-01-13
  • 45.
    Jonsson, E
    et al.
    Quantify Research, Stockholm, Sweden.
    Hansson-Hedblom, A
    Quantify Research, Stockholm, Sweden.
    Ljunggren, Ö
    Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden.
    Åkesson, K
    Department of Clinical Sciences, Clinical and Molecular Osteoporosis Unit, Lund University, Malmö, Sweden.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Kanis, J A
    University of Sheffield, Sheffield, UK; Catholic University of Australia, Melbourne, Australia.
    Borgström, F
    Quantify Research, Stockholm; Karolinska Institutet, Stockholm, Sweden.
    A health economic simulation model for the clinical management of osteoporosis2018In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 29, no 3, p. 545-555Article in journal (Refereed)
    Abstract [en]

    The objective was to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. Results showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings.

    INTRODUCTION: The purpose of this study is to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice.

    METHODS: The analysis was carried out using a model that simulates the individual patients considered for pharmacological treatment during 1 year and their projected osteoporosis treatment pathway, quality-adjusted life years (QALYs) and costs over their remaining lifetime. All patients regardless of treatment or no treatment were simulated. Information on current management of osteoporosis in terms of patient characteristics and treatment patterns were derived from a Swedish osteoporosis research database based on national registers and patient records. Current (standard) clinical management was compared with alternative scenarios mirroring Swedish treatment guidelines.

    RESULTS: The national burden in terms of lost QALYs was estimated at 14,993 QALYs and the total economic cost at €776M. Scenario analyses showed that 382-3864 QALYs could be gained at a cost/QALY ranging from cost-saving to €31368, depending on the scenario. The margin of investment, i.e. the maximum amount that could be invested in the healthcare system to achieve these improvements up to the limit of the willingness to pay/QALY, was estimated at €199M on a population level (€3,634/patient).

    CONCLUSIONS: The analysis showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. From a cost-effectiveness perspective, there is also considerable room for investment to achieve these improvements in the management of osteoporosis.

    The full text will be freely available from 2018-12-01 14:30
  • 46.
    Jufvas, Åsa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Human Adipocytes: Proteomic Approaches2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Type 2 diabetes is characterized by increased levels of glucose in the blood originating from insulin resistance in insulin sensitive tissues and from reduced pancreatic insulin production. Around 400 million people in the world are diagnosed with type 2 diabetes and the correlation with obesity is strong. In addition to life style induction of obesity and type 2 diabetes, there are indications of genetic and epigenetic influences. This thesis has focused on the characterization of primary human adipocytes, who play a crucial role in the development of type 2 diabetes.

    Histones are important proteins in chromatin dynamics and may be one of the factors behind epigenetic inheritance. In paper I, we characterized histone variants and posttranslational modifications in human adipocytes. Several of the specific posttranslational histone modifications we identified have been characterized in other cell types, but the majority was not previously known. Moreover, we identified a variant of histone H4 on protein level for the first time.

    In paper II, we studied specific histone H3 methylations in the adipocytes. We found that overweight is correlated with a reduction of H3K4me2 while type 2 diabetes is associated with an increase of H3K4me3. This shows a genome-wide difference in important chromatin modifications that could help explain the epidemiologically shown association between epigenetics and metabolic health.

    Caveolae is a plasma membrane structure involved in the initial and important steps of insulin signaling. In paper III we characterized the IQGAP1 interactome in human adipocytes and suggest that IQGAP1 is a link between caveolae and the cytoskeleton. Moreover, the amount of IQGAP1 is drastically lower in adipocytes from type 2 diabetic subjects compared with controls implying a potential role for IQGAP1 in insulin resistance.

    In conclusion, this thesis provides new insights into the insulin signaling frameworks and the histone variants and modifications of human adipocytes.

    List of papers
    1. Histone Variants and Their Post-Translational Modifications in Primary Human Fat Cells
    Open this publication in new window or tab >>Histone Variants and Their Post-Translational Modifications in Primary Human Fat Cells
    2011 (English)In: PLOS ONE, ISSN 1932-6203, Vol. 6, no 1Article in journal (Refereed) Published
    Abstract [en]

    Epigenetic changes related to human disease cannot be fully addressed by studies of cells from cultures or from other mammals. We isolated human fat cells from subcutaneous abdominal fat tissue of female subjects and extracted histones from either purified nuclei or intact cells. Direct acid extraction of whole adipocytes was more efficient, yielding about 100 mu g of protein with histone content of 60%-70% from 10 mL of fat cells. Differential proteolysis of the protein extracts by trypsin or ArgC-protease followed by nanoLC/MS/MS with alternating CID/ETD peptide sequencing identified 19 histone variants. Four variants were found at the protein level for the first time; particularly HIST2H4B was identified besides the only H4 isoform earlier known to be expressed in humans. Three of the found H2A potentially organize small nucleosomes in transcriptionally active chromatin, while two H2AFY variants inactivate X chromosome in female cells. HIST1H2BA and three of the identified H1 variants had earlier been described only as oocyte or testis specific histones. H2AFX and H2AFY revealed differential and variable N-terminal processing. Out of 78 histone modifications by acetylation/trimethylation, methylation, dimethylation, phosphorylation and ubiquitination, identified from six subjects, 68 were found for the first time. Only 23 of these modifications were detected in two or more subjects, while all the others were individual specific. The direct acid extraction of adipocytes allows for personal epigenetic analyses of human fat tissue, for profiling of histone modifications related to obesity, diabetes and metabolic syndrome, as well as for selection of individual medical treatments.

    Place, publisher, year, edition, pages
    Public Library of Science (PLoS), 2011
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-65933 (URN)10.1371/journal.pone.0015960 (DOI)000286512900014 ()
    Note

    Original Publication: Asa Jufvas, Peter Strålfors and Alexander Vener, Histone Variants and Their Post-Translational Modifications in Primary Human Fat Cells, 2011, PLOS ONE, (6), 1. http://dx.doi.org/10.1371/journal.pone.0015960 Licensee: Public Library of Science (PLoS) http://www.plos.org/

    Available from: 2011-02-28 Created: 2011-02-28 Last updated: 2016-03-08
    2. Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes.
    Open this publication in new window or tab >>Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes.
    Show others...
    2013 (English)In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 5, no 1, article id 15Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Epidemiological evidence indicates yet unknown epigenetic mechanisms underlying a propensity for overweight and type 2 diabetes. We analyzed the extent of methylation at lysine 4 and lysine 9 of histone H3 in primary human adipocytes from 43 subjects using modification-specific antibodies.

    RESULTS: The level of lysine 9 dimethylation was stable, while adipocytes from type 2 diabetic and non-diabetic overweight subjects exhibited about 40% lower levels of lysine 4 dimethylation compared with cells from normal-weight subjects. In contrast, trimethylation at lysine 4 was 40% higher in adipocytes from overweight diabetic subjects compared with normal-weight and overweight non-diabetic subjects. There was no association between level of modification and age of subjects.

    CONCLUSIONS: The findings define genome-wide molecular modifications of histones in adipocytes that are directly associated with overweight and diabetes, and thus suggest a molecular basis for existing epidemiological evidence of epigenetic inheritance.

    Place, publisher, year, edition, pages
    BioMed Central, 2013
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:liu:diva-99450 (URN)10.1186/1868-7083-5-15 (DOI)000329455000001 ()24004477 (PubMedID)
    Available from: 2013-10-18 Created: 2013-10-18 Last updated: 2017-12-06Bibliographically approved
  • 47.
    Jufvas, Åsa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Sjödin, Simon
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Lundqvist, Kim
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Amin, Risul
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Vener, Alexander V
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Strålfors, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Global differences in specific histone H3 methylation are associated with overweight and type 2 diabetes.2013In: Clinical Epigenetics, E-ISSN 1868-7083, Vol. 5, no 1, article id 15Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Epidemiological evidence indicates yet unknown epigenetic mechanisms underlying a propensity for overweight and type 2 diabetes. We analyzed the extent of methylation at lysine 4 and lysine 9 of histone H3 in primary human adipocytes from 43 subjects using modification-specific antibodies.

    RESULTS: The level of lysine 9 dimethylation was stable, while adipocytes from type 2 diabetic and non-diabetic overweight subjects exhibited about 40% lower levels of lysine 4 dimethylation compared with cells from normal-weight subjects. In contrast, trimethylation at lysine 4 was 40% higher in adipocytes from overweight diabetic subjects compared with normal-weight and overweight non-diabetic subjects. There was no association between level of modification and age of subjects.

    CONCLUSIONS: The findings define genome-wide molecular modifications of histones in adipocytes that are directly associated with overweight and diabetes, and thus suggest a molecular basis for existing epidemiological evidence of epigenetic inheritance.

  • 48.
    Karlsson, Cecilia
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
    Insulin Signalling in Human Adipocytes and its Interplay with beta-Adrenergic Control of Lipolysis2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [sv]

    The prevalence of obesity has over the last 40 years nearly tripled and obesity is one of the major risk factors of developing type 2 diabetes. Type 2 diabetes was formerly called adultonset diabetes but today, probably due to the rise in childhood obesity, it is also seen in children and adolescents. Type 2 diabetes is diagnosed when the body no longer can control the glucose levels in the blood. This is due to an insulin resistant state in the insulin responding tissues, liver, adipose and muscle and insufficient production of insulin in the pancreas. However, in spite of extensive research the mechanisms behind insulin resistance is still not known.

    The adipose tissue is believed to play a major role in the development of whole body insulin resistance. Adipocytes are the most important sites for storage of the high energy containing triacylglycerols. Insulin stimulation causes the adipocyte to increase the uptake of glucose and to reduce lipolysis: the hydrolysis of triacylglycerol and release of glycerol and fatty acids. The insulin signalling network is complex with numerous proteins involved. These signaling proteins not only transmit the insulin signal but also create negative and positive feedbackloops and induce cross talk between different parts of the network and with the signalling of other hormones. One important positive feedback in insulin signalling is the mTORC1 mediated feedback to phosphorylation of IRS1 at serine 307. In paper I we found that in human adipocytes this feedback is not likely catalysed by the assumed kinase S6K1. However we find an immunoprecipitate of mTOR to contain a ser307 phosphorylating kinase.

    Scaffolding proteins serve as docking sites for several proteins to promote protein-protein interactions that facilitate signal transduction. In paper II we demonstrate the existence of the scaffolding protein IQGAP1 in human adipocytes and that the expression of IQGAP1 is downregulated in type 2 diabetes. We reveal that IQGAP1 co-localises with caveolae, invaginations of the plasma membrane where the insulin receptor is situated, and that this interaction is increased upon insulin stimulation.

    In paper III we focus on the control of lipolysis, and sought to understand the interplay between insulin and beta-adrenergic stimulation. We demonstrated that the re-esterification of fatty acids is downregulated in type 2 diabetes causing an increased release of fatty acids from the cells. We showed that beta-adrenergic stimulation with isoproterenol induced a negative feedback via PKA/Epac1 -> PI3K -> PKB -> PDE3B that reduced the cAMP levels and thereby also reduced lipolysis. We also showed that insulin, in addition to its well-known anti-lipolytic effect, at high concentrations had a positive effect on lipolysis. In conclusion we reveal an intricate control of the stimulation as well as the inhibition of lipolysis induced by both isoproterenol and insulin.

    List of papers
    1. Phosphorylation of IRS1 at Serine 307 in Response to Insulin in Human Adipocytes Is Not Likely to be Catalyzed by p70 Ribosomal S6 Kinase
    Open this publication in new window or tab >>Phosphorylation of IRS1 at Serine 307 in Response to Insulin in Human Adipocytes Is Not Likely to be Catalyzed by p70 Ribosomal S6 Kinase
    Show others...
    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4Article in journal (Refereed) Published
    Abstract [en]

    The insulin receptor substrate-1 (IRS1) is phosphorylated on serine 307 (human sequence, corresponding to murine serine 302) in response to insulin as part of a feedback loop that controls IRS1 phosphorylation on tyrosine residues by the insulin receptor. This in turn directly affects downstream signaling and is in human adipocytes implicated in the pathogenesis of insulin resistance and type 2 diabetes. The phosphorylation is inhibited by rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR) in complex with raptor (mTORC1). The mTORC1-downstream p70 ribosomal protein S6 kinase (S6K1), which is activated by insulin, can phosphorylate IRS1 at serine 307 in vitro and is considered the physiological protein kinase. Because the IRS1 serine 307-kinase catalyzes a critical step in the control of insulin signaling and constitutes a potential target for treatment of insulin resistance, it is important to know whether S6K1 is the physiological serine 307-kinase or not. We report that, by several criteria, S6K1 does not phosphorylate IRS1 at serine 307 in response to insulin in intact human primary adipocytes: (i) The time-courses for phosphorylation of S6K1 and its phosphorylation of S6 are not compatible with the phosphorylation of IRS1 at serine 307; (ii) A dominant-negative construct of S6K1 inhibits the phosphorylation of S6, without effect on the phosphorylation of IRS1 at serine 307; (iii) The specific inhibitor of S6K1 PF-4708671 inhibits the phosphorylation of S6, without effect on phosphorylation of IRS1 at serine 307. mTOR-immunoprecipitates from insulin-stimulated adipocytes contains an unidentified protein kinase specific for phosphorylation of IRS1 at serine 307, but it is not mTOR or S6K1.

    Place, publisher, year, edition, pages
    Public Library of Science, 2013
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-93257 (URN)10.1371/journal.pone.0059725 (DOI)000317717300032 ()
    Note

    Funding Agencies|Swedish Diabetes Fund||Novo Nordic Foundation||University of Linkoping||Swedish Research Council||

    Available from: 2013-05-28 Created: 2013-05-28 Last updated: 2018-04-27
    2. Scaffolding protein IQGAP1: an insulin-dependent link between caveolae and the cytoskeleton in primary human adipocytes?
    Open this publication in new window or tab >>Scaffolding protein IQGAP1: an insulin-dependent link between caveolae and the cytoskeleton in primary human adipocytes?
    Show others...
    2016 (English)In: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 473, no 19, p. 3177-3188Article in journal (Refereed) Published
    Abstract [en]

    The ubiquitously expressed IQ motif-containing GTPase activating protein-1 (IQGAP1) is a scaffolding protein implicated in an array of cellular functions, in particular by binding to cytoskeletal elements and signaling proteins. A role of IQGAP1 in adipocytes has not been reported. We therefore investigated the cellular IQGAP1 interactome in primary human adipocytes. Immunoprecipitation and quantitative mass spectrometry identified caveolae and caveolae-associated proteins as the major IQGAP1 interactors alongside cytoskeletal proteins. We confirmed co-localization of IQGAP1 with the defining caveolar marker protein caveolin-1 by confocal microscopy and proximity ligation assay. Most interestingly, insulin enhanced the number of IQGAP1 interactions with caveolin-1 by five-fold. Moreover, we found a significantly reduced abundance of IQGAP1 in adipocytes from patients with type 2 diabetes compared with cells from nondiabetic control subjects. Both the abundance of IQGAP1 protein and mRNA were reduced, indicating a transcriptional defect in diabetes. Our findings suggest a novel role of IQGAP1 in insulin-regulated interaction between caveolae and cytoskeletal elements of the adipocyte, and that this is quelled in the diabetic state.

    Place, publisher, year, edition, pages
    Portland Press, 2016
    National Category
    Cell Biology
    Identifiers
    urn:nbn:se:liu:diva-131958 (URN)10.1042/BCJ20160581 (DOI)000393755500017 ()27458251 (PubMedID)
    Note

    Funding agencies: University of Linkoping; 3-year program at the Swedish Diabetes Fund; 5-year program at the Swedish Research Council

    Available from: 2016-10-12 Created: 2016-10-12 Last updated: 2018-04-27Bibliographically approved
  • 49.
    Keselman, Boris
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Vergara Valgañon, Marta
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nyberg, Sofia
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A randomized cross-over study of the acute effects of running 5 km on glucose, insulin, metabolic rate, cortisol and Troponin T2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0179401Article in journal (Refereed)
    Abstract [en]

    Background We aimed to study the impact by running 5 km, at maximal speed, on the normal variations of metabolic variables related to glucose, insulin, insulin sensitivity, cortisol, glucagon, Troponin T and metabolic rate. Material and methods Five women and 12 men 25.7 +/- 5.2 years of age with a body-mass-index of 22.5 +/- 2.3 kg/m(2) where recruited to run 5 km at individual maximal speed in the morning, and to a corresponding day of rest, followed by standardized breakfast and lunch meals. Blood sampling and measurement of indirect calorimetry were done before and after meals. The participants were randomized regarding the order of the two trial-days in this cross-over study. Results Insulin and cortisol levels were higher, and insulin sensitivity was lower, on the race-day compared with the day of rest (linear mixed model: pamp;lt;0.0001 for all three analyses). However, glucose levels and metabolic rate did not differ between the two trial days (p = 0.29 and p = 0.53, respectively). When analyzing specific time-points we found that glucose increased from 5.01 +/- 0.37 mmol/l to 6.36 +/- 1.3 mmol/l, pamp;lt;0.0001, by running, while serum insulin concomitantly increased from 42 21 to 90 54 pmo1/1, pamp;lt;0.0001. In accordance, the QUICKI index of serum sensitivity, 1/(log(10)insulin+log(10)glucose), was lowered post-race, pamp;lt;0.0001. Serum cortisol levels increased from 408 137 nmol/l to 644 171 nmol/l, pamp;lt;0.0001, post-race while serum glucagon levels were unaffected. Troponin T was detectable in serum post-race in 12 out of the 17 participants and reached or surpassed the clinical reference level of 15 ng/l in three subjects. Post-race electrocardiograms displayed no pathologies. Conclusions Relatively short running-races can apparently induce a reduction in insulin sensitivity that is not fully compensated by concomitantly increased insulin secretion intended to ensure euglycemia. Since also Troponin T was detected in plasma in a majority of the participants, our data suggest that it is possible to induce considerable metabolic stress by running merely 5 km, when striving for maximal speed.

  • 50.
    Knip, Mikael
    et al.
    University of Helsinki, Finland; Helsinki University Hospital, Finland.
    Akerblom, Hans K.
    University of Helsinki, Finland.
    Al Taji, Eva
    Charles University of Prague, Czech Republic.
    Becker, Dorothy
    University of Pittsburgh, PA USA.
    Bruining, Jan
    Sophia Childrens University Hospital, Netherlands.
    Castano, Luis
    University of Basque Country, Spain.
    Danne, Thomas
    Kinder-und Jugendkrankenhaus–Auf der Bult, Hannover, Germany.
    de Beaufort, Carine
    Centre Hospital Luxembourg, Luxembourg.
    Dosch, Hans-Michael
    University of Toronto, Canada.
    Dupre, John
    University of Western Ontario, Canada.
    Fraser, William D.
    University of Sherbrooke, Canada.
    Howard, Neville
    Childrens Hospital Westmead, Australia.
    Ilonen, Jorma
    University of Turku, Finland; Turku University Hospital, Finland.
    Konrad, Daniel
    Kinder and Jugendkrankenhaus Auf Der Bult, Germany; University of Childrens Hospital Zurich, Switzerland.
    Kordonouri, Olga
    Kinder and Jugendkrankenhaus Auf Der Bult, Germany.
    Krischer, Jeffrey P.
    University of S Florida, FL USA.
    Lawson, Margaret L.
    Childrens Hospital Eastern Ontario, Canada.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Madacsy, Laszlo
    Semmelweis University, Hungary.
    Mahon, Jeffrey L.
    University of Western Ontario, Canada.
    Ormisson, Anne
    Tartu University, Estonia.
    Palmer, Jerry P.
    University of Washington, WA USA.
    Pozzilli, Paolo
    University of Campus Biomed Rome, Italy.
    Savilahti, Erkki
    University of Helsinki, Finland.
    Serrano-Rios, Manuel
    CIBERDEM, Spain.
    Songini, Marco
    St Michelle Hospital, Italy.
    Taback, Shayne
    University of Manitoba, Canada.
    Vaarala, Outi
    University of Helsinki, Finland; AstraZeneca, Sweden.
    White, Neil H.
    Washington University, MO USA.
    Virtanen, Suvi M.
    National Institute Health and Welf, Finland.
    Wasikowa, Renata
    Medical Academic Wroclaw, Poland.
    Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial2018In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 319, no 1, p. 38-48Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.

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