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  • 1.
    Akesson, Karin
    et al.
    Ryhov County Hospital, Sweden; Jonköping County Council, Sweden; University of Jonköping, Sweden.
    Hanberger, Lena
    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 Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    The influence of age, gender, insulin dose, BMI, and blood pressure on metabolic control in young patients with type 1 diabetes2015In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 16, no 8, p. 581-586Article in journal (Refereed)
    Abstract [en]

    ObjectiveTo explore the relationship between certain clinical variables and metabolic HbA1c at diagnosis correlated to HbA1c at follow-up (p less than 0.001). There was a clear gender difference regarding HbA1c. Girls had higher values both at diagnosis and at follow-up (p less than 0.001). Girls also had lower BMI and pH at diagnosis than boys (p less than 0.001). In contrast, girls with the highest body mass index (BMI) at follow-up had higher mean HbA1c at follow-up in 2010 (p less than 0.001). Having a mother and/or a father with high BMI implied higher HbA1c at diagnosis (p less than 0.003). ConclusionsHbA1c at diagnosis seems to predict metabolic control years later. There is a gender difference at diagnosis as female patients have higher HbA1c than males at diagnosis as well as at follow up. As metabolic control is very much correlated to complications there is a need to early identify patients at risk of poor metabolic control. Even though we do not know whether a high HbA1c level is mainly due to severity of the disease or to behavioral patterns, new ways to treat and support these children, especially girls, are needed.

  • 2.
    Andersson, C
    et al.
    Lund University, Sweden .
    Vaziri-Sani, F
    Lund University, Sweden .
    Delli, A J.
    Lund University, Sweden .
    Lindblad, B
    Queen Silvia Childrens Hospital, Sweden .
    Carlsson, A
    Lund University, Sweden .
    Forsander, G
    Queen Silvia Childrens Hospital, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Marcus, C
    Karolinska Institute, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ivarsson, S A.
    Lund University, Sweden .
    Lernmark, A
    Lund University, Sweden .
    Elding Larsson, H
    Lund University, Sweden .
    Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes2013In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, no 2, p. 97-105Article in journal (Refereed)
    Abstract [en]

    Andersson C, Vaziri-Sani F, Delli AJ, Lindblad B, Carlsson A, Forsander G, Ludvigsson J, Marcus C, Samuelsson U, Ivarsson SA, Lernmark A, Elding Larsson H, the BDD Study group. Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes. Pediatric Diabetes 2013: 14: 97-105. Objective To establish the diagnostic sensitivity of and the relationships between autoantibodies to all three Zinc transporter 8 (Zinc transporter 8 autoantibody to either one, two, or all three amino acid variants at position 325, ZnT8A) variants to human leukocyte antigen (HLA)-DQ and to autoantibodies to glutamic acid decarboxylase (GADA), insulinoma-associated protein 2 (IA-2A), and insulin (IAA). Methods We analyzed 3165 patients with type 1 diabetes (T1D) in the Better Diabetes Diagnosis study for HLA-DQ genotypes and all six autoantibodies (ZnT8RA, arginine 325 Zinc transporter 8 autoantibody; ZnT8WA, tryptophan 325 Zinc transporter 8 autoantibody; ZnT8QA, glutamine 325 Zinc transporter 8 autoantibody; GADA, IA-2A, and IAA). Results ZnT8A was found in 65% of the patients and as many as 108 of 3165 (3.4%) had 13 ZnT8A alone. None had ZnT8QA alone. Together with GADA (56%), IA-2A (73%), and IAA (33%), 93% of the T1D patients were autoantibody positive. All three ZnT8A were less frequent in children below 2 yr of age (pandlt;0.0001). All three ZnT8A were associated with DQA1-B1*X-0604 (DQ6.4) and DQA1-B1*03-0302 (DQ8). ZnT8WA and ZnT8QA were negatively associated with DQA1-B1*05-02 (DQ2). Conclusions Analysis of ZnT8A increased the diagnostic sensitivity of islet autoantibodies for T1D as only 7% remained islet autoantibody negative. The association between DQ6.4 and all three ZnT8A may be related to ZnT8 antigen presentation by the DQ6.4 heterodimer.

  • 3.
    Andersson, Cecilia
    et al.
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Kolmodin, Martin
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Ivarsson, Sten-Anders
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Carlsson, Annelie
    Department of Pediatrics, Lund University, Sweden.
    Forsander, Gun
    Department of Pediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Lindblad, Bengt
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Kockum, Ingrid
    Department of Clinical Neurosciences, Karolinska Institute, Stockholm, Sweden.
    Marcus, Claude
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology Karolinska Institute, Stockholm, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ortqvist, Eva
    Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
    Lernmark, Ake
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Elding Larsson, Helena
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Törn, Carina
    Department of Clinical Sciences, Lund University, Malmö, Sweden.
    Islet cell antibodies (ICA) identify autoimmunity in children with new onset diabetes mellitus negative for other islet cell antibodies2014In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 15, no 5, p. 336-344Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of this study was to explore whether islet cell antibodies (ICA) could be identified in children with newly onset diabetes mellitus but negative for autoantibodies against glutamic acid decarboxylase (GADA), islet antigen-2 (IA-2A), insulin (IAA), or any of the three variants with arginine (R), tryptophan (W), or glutamine (Q) at position 325 of the zinc transporter 8 (ZnT8A).

    METHODS: A population-based analysis of autoantibodies was performed from 1 May 2005 to 2 September 2010 in Swedish children newly diagnosed with diabetes. ICA was analyzed with an enzyme-linked immunosorbent assay and if positive, reanalyzed in the classical ICA immunofluorescence assay, in 341 samples among 3545 children who had been tested negative for all of GADA, IA-2A, IAA, or ZnT8A (R, W, Q).

    RESULTS: An isolated positivity for ICA was identified in 5.0% (17/341) of the newly diagnosed children. The levels of ICA in positive subjects ranged from 3 to 183 JDF-U (median 30). This finding increased the diagnostic sensitivity of islet autoimmunity as 3204/3545 patients (90.4%) were islet autoantibody positive without the ICA analyses and 3221 patients (90.9%) were positive with the inclusion of ICA.

    CONCLUSIONS: The finding of an isolated positivity for ICA despite negativity for GADA, IA-2A, IAA, and ZnT8A (R, W, Q) suggests that still another yet unidentified autoantigen(s) may contribute to the ICA immunofluorescence. Hence, ICA is important to analyze in type 1 diabetes children and adolescents that would otherwise be islet autoantibody negative.

  • 4.
    Anderzen, Johan
    et al.
    Ryhov County Hospital, Sweden.
    Samuelsson, Ulf
    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.
    Gudbjornsdottir, Soffia
    University of Gothenburg, Sweden.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Akesson, Karin
    Ryhov County Hospital, Sweden; Futurum, Australia; Jonköping Academic Improvement Health and Welf, Germany.
    Teenagers with poor metabolic control already have a higher risk of microvascular complications as young adults2016In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 30, no 3, p. 533-536Article in journal (Refereed)
    Abstract [en]

    Aims: To evaluate how HbA1c in adolescents with type 1 diabetes affects microvascular complications in young adults. Methods: All individuals registered in the Swedish paediatric diabetes quality registry (SWEDIABKIDS) 13-18 years of age, and as adults registered in the Swedish National Diabetes Registry (NDR) in both the years 2011 and 2012 were included, in total 4250 individuals. Results: Of the individuals with mean HbA1c >78 mmol/mol in SWEDIABKIDS 83.4% had retinopathy, 15.8% had microalbuminuria and 4.9% had macroalbuminuria in NDR. The logistic regression analysis showed that the OR to develop macroalbuminuria as a young adult was significantly higher in the group with mean HbA1c >78 mmol/mol in SWEDIABKIDS (p < 0.05). Among the patients with mean HbA1c above 78 mmol/mol in both registries there was a significantly higher proportion that had retinopathy, microalbuminuria (p < 0.001) and/or macroalbuminuria (p < 0.01) compared to the group with HbA1c below 57 mmol/mol in both registries. Only 6.5% of the persons in this study were over 30 years of age. Conclusions: Paediatric diabetes teams working with teenagers must be aware of the impact of good metabolic control during adolescence, and should intensify the care during this vulnerable period of life to reduce the risk of microvascular complications in young adults.

  • 5.
    Beraki, Å
    et al.
    Linköping University.
    Magnuson, A.
    Örebro University Hospital, Sweden .
    Särnblad, S.
    Örebro University Hospital, Sweden; Örebro University, Sweden.
    Åman, J.
    Örebro University Hospital, Sweden; Örebro University, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Increase in physical activity is associated with lower HbA1c levels in children and adolescents with type 1 diabetes: results from a cross-sectional study based on the Swedish pediatric diabetes quality registry (SWEDIABKIDS)2014In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 105, no 1, p. 119-125Article in journal (Refereed)
    Abstract [en]

    AIMS:

    To evaluate the associations between physical activity (PA) and metabolic control, measured by glycated hemoglobin (HbA1c), in a large group of children and adolescents with type 1 diabetes.

    METHODS:

    Cross-sectional analysis of data from 4655 patients, comparing HbA1c values with levels of physical activity. The data for the children and adolescents were obtained from the Swedish pediatric diabetes quality registry, SWEDIABKIDS. The patients were 7-18 years of age, had type 1 diabetes and were not in remission. Patients were grouped into five groups by frequency of PA.

    RESULTS:

    Mean HbA1c level was higher in the least physically active groups (PA0: 8.8% ± 1.5 (72 ± 16 mmol/mol)) than in the most physically active groups (PA4: 7.7% ± 1.0 (60 ± 11 mmol/mol)) (p<0.001). An inverse dose-response association was found between PA and HbA1c (β: -0.30, 95% CI: -0.34 to -0.26, p<0.001). This association was found in both sexes and all age groups, apart from girls aged 7-10 years. Multiple regression analysis revealed that the relationship remained significant (β: -0.21, 95% CI: -0.25 to -0.18, p<0.001) when adjusted for possible confounding factors.

    CONCLUSIONS:

    Physical activity seems to influence HbA1c levels in children and adolescents with type 1 diabetes. In clinical practice these patients should be recommended daily physical activity as a part of their treatment.

  • 6.
    Boman, Krister
    et al.
    Barncancerforskningsenheten Karolinska sjukhuset, Stockholm.
    Viksten, Jonas
    Avd för Psykologi Stockholms Universitet.
    Kogner, Per
    Barncancerforskningsenheten Karolinska sjukhuset, Stockholm.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Serious illness in childhood: the different threats of cancer and diabetes from a parent perspective.2004In: Journal of Pediatrics, ISSN 0022-3476, E-ISSN 1097-6833, Vol. 145, p. 373-379Article in journal (Refereed)
    Abstract [en]

    Objectives To compare the incidence of disease-related distress symptoms in parents of children with cancer and diabetes. Study design A total of 675 parents of patients with cancer, patients with diabetes, and control subjects were assessed for 11 distress symptom clusters. Patient and control parent mean differences were tested by 2-tailed t tests, illness groups were compared by means of analysis of variance. Distress variations as a function of time since diagnosis were examined by regression analysis. Results The distress levels of patient parents exceeded those of control parents for global distress (P < .0001) and for most symptom subcategories. Distress levels of parents of patients with cancer (CP) significantly exceeded those of parents of patients with diabetes (DP) in anxiety (P < .0001), physical and psychologic distress (P < .0001), depression (P < .005), and loneliness (P < .05). Levels in DP matched those of CP in uncertainty, loss of control/the patient, self-esteem, disease-related fear, and sleep disturbances. Distress levels were lower in CP most distant hi time from diagnosis, whereas DP showed a reversed trend. Conclusions Parental distress patterns in childhood illness depend on illness type and time passed since diagnosis. Symptom profiles verify the need for psyehosocial attention at the initial shock after the cancer diagnosis and indicate long-term consequences for many parents. In pediatric diabetes, the persistence or intensification of distress over time is of specific clinical relevance.

  • 7.
    Delli, Ahmed J
    et al.
    Lund University, Sweden .
    Vaziri-Sani, Fariba
    Lund University, Sweden .
    Lindblad, Bengt
    University of Gothenburg, Sweden .
    Elding-Larsson, Helena
    Lund University, Sweden .
    Carlsson, Annelle
    Lund University, Sweden .
    Forsander, Gun
    Sahlgrens University Hospital, Sweden .
    Ivarsson, Sten A
    Lund University, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Kockum, Ingrid
    Karolinska Institute, Sweden .
    Marcus, Claude
    Karolinska Institute, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ortqvist, Eva
    Karolinska Institute, Sweden .
    Groop, Leif
    Lund University, Sweden .
    P Bondinas, George
    Epirus Institute Technology, Greece .
    Papadopoulos, George K
    Epirus Institute Technology, Greece .
    Lernmark, Ake
    Lund University, Sweden .
    Zinc Transporter 8 Autoantibodies and Their Association With SLC30A8 and HLA-DQ Genes Differ Between Immigrant and Swedish Patients With Newly Diagnosed Type 1 Diabetes in the Better Diabetes Diagnosis Study2012In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 61, no 10, p. 2556-2564Article in journal (Refereed)
    Abstract [en]

    We examined whether zinc transporter 8 autoantibodies (ZnT8A; arginine ZnT8-RA, tryptophan ZnT8-WA, and glutamine ZnT8-QA variants) differed between immigrant and Swedish patients due to different polymorphisms of SLC30A8, HLA-DQ, or both. Newly diagnosed autoimmune (andgt;= 1 islet autoantibody) type 1 diabetic patients (n = 2,964, andlt;18 years, 55% male) were ascertained in the Better Diabetes Diagnosis study. Two subgroups were identified: Swedes (n = 2,160, 73%) and immigrants (non-Swedes; n = 212, 7%). Non-Swedes had less frequent ZnT8-WA (38%) than Swedes (50%), consistent with a lower frequency in the non-Swedes (37%) of SLC30A8 CT+TT (RW+WW) genotypes than in the Swedes (54%). ZnT8-RA (57 and 58%, respectively) did not differ despite a higher frequency of CC (RR) genotypes in non-Swedes (63%) than Swedes (46%). We tested whether this inconsistency was due to HLA-DQ as 2/X (2/2; 2/y; y is anything but 2 or 8), which was a major genotype in non-Swedes (40%) compared with Swedes (14%). In the non-Swedes only, 2/X (2/2; 2/y) was negatively associated with ZnT8-WA and ZnT8-QA but not ZnT8-RA. Molecular simulation showed nonbinding of the relevant ZnT8-R peptide to DQ2, explaining in part a possible lack of tolerance to ZnT8-R. At diagnosis in non-Swedes, the presence of ZnT8-RA rather than ZnT8-WA was likely due to effects of HLA-DQ2 and the SLC30A8 CC (RR) genotypes.

  • 8.
    Elding Larsson, Helena
    et al.
    Lund University.
    Vehik, Kendra
    University of S Florida.
    Bell, Ronny
    Wake Forest University.
    Dabelea, Dana
    Colorado School Public Heatlh.
    Dolan, Lawrence
    University of Cincinnati.
    Pihoker, Catherine
    University of Washington.
    Knip, Mikael
    Tampere University Hospital.
    Veijola, Riitta
    University of Oulu.
    Lindblad, Bengt
    University of Gothenburg.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Holl, Reinhard
    University of Ulm.
    J Haller, Michael
    University of Florida.
    Reduced Prevalence of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Young Children Participating in Longitudinal Follow-Up2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 11, p. 2347-2352Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type I. diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged andlt;2 and andlt;5 years compared with population-based incidence studies and registries. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Symptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register). less thanbrgreater than less thanbrgreater thanRESULTS-A total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children andlt;2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P andlt; 0.0001; Swediabkids, P = 0.02; SEARCH, P andlt; 0.0001; Finnish Register, P andlt; 0.0001). The prevalence of DKA in TEDDY children diagnosed at andlt;5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) (P andlt; 0.0001) and the German DPV Register (32.2%) (P andlt; 0.0001) but not compared with Swediabkids or the Finnish Register. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-Participation in the TEDDY study is associated with reduced risk of DMA at diagnosis of type 1 diabetes in young children.

  • 9.
    Ernerudh, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Effect of photopheresis on lymphocyte population in children with newly diagnosed type 1 diabetes2004In: Clinical and Diagnostic Laboratory Immunology, ISSN 1071-412X, Vol. 11, no 5, p. 856-861Article in journal (Refereed)
    Abstract [en]

    In recent years photopheresis has been claimed to be an effective form of immunomodulation. It has also been shown to have an effect on the disease process at the onset of type 1 diabetes. In a double-blind, placebo-controlled randomized study, we analyzed if the effect of photopheresis in children with newly diagnosed diabetes is related to changes in the balance of lymhocyte populations. We also analyzed if lymphocyte subsets were related to recent infection, mild or aggressive disease manifestations, heredity, or gender. Nineteen children received active treatment with photopheresis, while 21 children received sham pheresis (placebo group). No influence of a history of previous infection, heredity, or certain clinical parameters on lymphocyte subsets was found. At the onset of type 1 diabetes, girls showed a higher proportion and a larger number of T cells (CD3+) and T-helper cells (CD4+) and a higher proportion of naïve CD4 +CD45RA+ cells. In the placebo group, an increase in the number of subsets with the activated phenotype in both the CD4 (CD29 +) and the CD8 (CD11a+) compartments was noted during the course of the study. These changes did not occur in the photopheresis group. No relation between lymphocyte subsets and clinical outcome was found 1 year after the treatment with photopheresis. In conclusion, we found no major effect of photopheresis on lymphocyte populations in a group of children with newly diagnosed type 1 diabetes. However, in the placebo group the proportions of activated CD4 and CD8 cells increased over time. Since these changes did not occur in the actively treated group, our findings suggest that photopheresis may have some suppressive effects.

  • 10.
    Hanberger, Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Akesson, K.
    County Hospital Ryhov, Sweden Jonköping University, Sweden Jonköping University, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Glycated haemoglobin variations in paediatric type 1 diabetes: the impact of season, gender and age2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 4, p. 398-403Article in journal (Refereed)
    Abstract [en]

    AimTo study whether monthly variations in type 1 diabetes incidence are related to monthly glycated haemoglobin (HbA1c) levels at diagnosis and if high HbA1c at diagnosis is related to certain clinical variables at diagnosis and during the clinical course of the disease. MethodsData from 4430 boys and 3590 girls registered in the Swedish paediatric diabetes quality registry, Swedish paediatric diabetes quality registry, from 2000 to 2010 were analysed. ResultsMonth of onset varied (pless than0.001), with 53% diagnosed during September to February, and mean HbA1c at diagnosis was highest in May (10.9%, 96mmol/mol) and lowest in (October 9.4%, 88mmol/mol) (pless than0.001). Girls showed higher HbA1c at onset than boys (pless than0.001). More than half (53%) with an annual mean HbA1c of greater than9.3% (78mmol/mol) and 4% of those with an annual mean of less than7.4% (57mmol/mol) in 2007 had greater than9.3% (78mmol/mol) in 2010. ConclusionPatients with high HbA1c levels during a certain period have the same high levels several years later. This group, perhaps including those with high HbA1c level at diagnosis, may need more intensive care, including extra support from the diabetes teams and other forms of medical treatment.

  • 11.
    Hanberger, Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Birkebaek, Niels
    Department of Paediatrics, Aarhus, Aarhus University Hospital, Skejby, Denmark.
    Bjarnason, Ragnar
    Children’s Medical Center, Landspítali University Hospital and Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
    Drivvoll, Ann Kristin
    Woman and Children’s Division, Department of Paediatric Medicine, Norwegian Childhood Diabetes Registry, Oslo University Hospital, Oslo, Norway.
    Johansen, Anders
    Department of Paediatrics, Herlev University Hospital, Herlev, Denmark.
    Skrivarhaug, Torild
    Woman and Children’s Division, Department of Paediatric Medicine, Norwegian Childhood Diabetes Registry, Oslo University Hospital, Oslo, Norway / Woman and Children’s Division, Department of Paediatric Medicine, Oslo University Hospital, Oslo, Norway.
    Thorsson, Arni V
    Children’s Medical Center, Landspítali University Hospital and Faculty of Medicine, University of Iceland, Reykjavík, Iceland.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Childhood diabetes in the nordic countries: a comparison of quality registries.2014In: Journal of diabetes science and technology, ISSN 1932-2968, Vol. 8, no 4, p. 738-44Article in journal (Refereed)
    Abstract [en]

    In 2008 a Nordic collaboration was established between the quality registries in Denmark, Iceland, Norway, and Sweden to improve quality of care for children with diabetes. This study aimed to describe those registries and confirm that the registry variables are comparable. Selected variables were used to demonstrate outcome measurements. The organization of the registries and methodology are described. Cross-sectional data for patients between birth and 14.9 years with type 1 diabetes mellitus in 2009 (n = 6523) from 89 centers were analyzed. Variables were age, gender, and diabetic ketoacidosis at onset, together with age, gender, HbA1c, insulin regimen, and severe hypoglycemia at follow-up in 2009. All 4 registries use a standardized registration at the onset of diabetes and at follow-up, conducted at the local pediatric diabetes centers. Methods for measuring HbA1c varied as did methods of registration for factors such as hypoglycemia. No differences were found between the outcomes of the clinical variables at onset. Significant variations were found at follow-up for mean HbA1c, the proportion of children with HbA1c < 57 mmol/mol (NGSP/DCCT 7.4%), (range 15-31%), the proportion with insulin pumps (range 34-55%), and the numbers with severe hypoglycemia (range 5.6-8.3/100 patient years). In this large unselected population from 4 Nordic countries, a high proportion did not reach their treatment target, indicating a need to improve the quality of pediatric diabetes care. International collaboration is needed to develop and harmonize quality indicators and offers possibilities to study large geographic populations, identify problems, and share knowledge.

  • 12.
    Hanberger, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    The influence of process, structure and policy on Haemoglobin A1c levels in treatment of children and adolescents with type 1 diabetes2012In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 96, no 3, p. 331-338Article in journal (Refereed)
    Abstract [en]

    Objective: We aimed to identify factors for improvements of mean A1C at centres treating children and adolescents with diabetes.

    research Design and methods: Through data from the Swedish paediatric diabetes quality registry, SWEDIABKIDS, five centres with the lowest mean A1C (Low group), five with the highest (High group), and five with the largest decrease in centre mean A1C (Decrease group) were identified. The diabetes team members completed a questionnaire, response rate 85%, (109/128) and reported team structure and process. Open-ended questions regarding messages to patients about important diabetes matters were analysed with summative content analysis.

    Results: Compared to the High group, the Low and Decrease groups showed shorter professional experience and lower proportion of special diabetes-educated team members, and higher compliance with guidelines. Trends for higher mean insulin dose, larger centre size and larger team size were found. The content analysis indicated that the Low and Decrease groups gave a clear message and had lower A1C target value. The team members in these groups were engaged, had a positive attitude and a perception of a well-functioning team. The High group gave a vague message, needed more frames and had a perception of lack of cooperation in the team.

    Conclusions: The team members' approach seems to affect metabolic control in children and adolescents. The team members need to be aware of their approach and how it affects patients and parents, and also of the importance of the possibility of using resources and competence within the team.

  • 13.
    Hanberger, Lena
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics .
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindblad, Bengt
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    AlC in children and adolescents with diabetes in relation to certain clinical parameters - The Swedish Childhood Diabetes Registry SWEDIABKIDS2008In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 31, no 5, p. 927-929Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - We explored the relationship between AlC and insulin regimen, duration of diabetes, age, sex, and BMI as well as the differences between clinical mean AlC levels at pediatric diabetes clinics in Sweden. RESEARCH DESIGN AND METHODS - Data from 18,651 clinical outpatient visits (1,033 girls and 1,147 boys) at 20 pediatric clinics during 2001 and 2002 registered in the Swedish Childhood Diabetes Registry SWEDIABKIDS, a national quality registry, were analyzed. RESULTS - AlC was < 7.0% (target value similar to 8% per Diabetes Control and Complications Trial/National Glycohemoglobin Standardization Program standards) at 35% of the visits. Girls had significantly higher mean AlC than boys during adolescence. High mean AlC was correlated with high mean insulin dose, long duration of diabetes, and older age. Mean AlC varied between clinics (6.8-8.2%). Differences between centers could not be explained by differences in diabetes duration, age, BMI, or insulin dose. CONCLUSIONS - Adolescents with a high insulin dose and a long duration of diabetes, especially girls, need to be focused on, Differences in mean values between centers remained inexplicable and require further investigation.

  • 14.
    Holmqvist, Britt-Marie
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Löfman, Owe
    Institute of Mathematical Science and Technology, The Norwegian University of Life Sciences, Aas, Norway.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    A low incidence of Type 1 diabetes between 1977 and 2001 in south-eastern Sweden in areas with high population density and which are more deprived2008In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 25, no 3, p. 255-260Article in journal (Refereed)
    Abstract [en]

    Aims  To explore how socioeconomic factors and population density may contribute to the geographical variation of incidence of Type 1 diabetes in children in south-eastern Sweden.

    Method  All children diagnosed with Type 1 diabetes in south-eastern Sweden during 1977–2001 were defined geographically to their place of residence and were allocated x and y coordinates in the national grid. The population at risk and socioeconomic data were aggregated in 82 000 200-m squares and geocoded likewise. A socioeconomic index was calculated using a signed χ2 method. Rural–urban gradients were defined by overlay analysis in a geographic information system.

    Results  The incidence during the past 25 years has been rising steadily, particularly in the last 6 years. The incidence was highest in areas with a high proportion of small families, of families with a high family income and better education, and this was found both at the time of diagnosis and at the time of birth. In the rural–urban analysis, the lowest incidence was found in the urban area with > 20 000 inhabitants, where there was also a higher frequency of deprivation.

    Conclusions  Our findings indicate that geographical variations in incidence rates of Type 1 diabetes in children are associated with socioeconomic factors and population density, although other contributing factors remain to be explained.

  • 15.
    Hoven, Emma
    et al.
    Astrid Lindgren Childrens Hospital.
    Anclair, Malin
    Astrid Lindgren Childrens Hospital.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Kogner, Per
    Astrid Lindgren Childrens Hospital.
    Boman, Krister K
    Astrid Lindgren Childrens Hospital.
    The Influence of Pediatric Cancer Diagnosis and Illness Complication Factors on Parental Distress2008In: Journal of pediatric hematology/oncology (Print), ISSN 1077-4114, E-ISSN 1536-3678, Vol. 30, no 11, p. 807-814Article in journal (Refereed)
    Abstract [en]

    Objective: We investigated how primary diagnosis and risk for diagnosis-related complication factors influence parental distress after a childs cancer diagnosis

    Methods: We used a model in which "complicated childhood cancers" were grouped into 1 category after identifying a set of potentially influential illness complication variables. This category included central nervous system tumors, acute myeloid leukemia, and bone tumors. Parental distress in that category (n = 144) was compared with distress after acute lymphoblastic leukemia (n = 177) in the child. In addition, comparisons were made between parents of the specific diagnosis groups. A multidimensional questionnaire assessing symptoms of distress was used.

    Results: Parents in the complicated cancer category showed significantly heightened disease-related fear, anxiety, depression, loss of control, late effects-related uncertainty, and poorer self-esteem compared with parents of children with acute lymphoblastic leukemia. Significantly heightened parental distress was associated with the child having been treated with cranial irradiation.

    Conclusions: Relatively heightened distress in parents of children with complicated cancer is influenced by diagnosis-related factors like an intricate prediagnostic phase, and uncertainty about late effects. Heightened vulnerability to distress signals exceptional needs for support and information among parents of children treated for central nervous system or bone tumors.

  • 16.
    Hyllienmark, Lars
    et al.
    Department of Clinical Neurophysiology, Karolinska Hospital, Stockholm, Sweden.
    Golster, Helena
    Linköping University, Department of Neuroscience and Locomotion, Clinical Neurophysiology. Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Samuelsson, Ulf
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nerve conduction defects are retarded by tight metabolic control in type I diabetes2001In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 24, no 2, p. 240-246Article in journal (Refereed)
    Abstract [en]

    This follow-up study examines whether the development of nerve dysfunction is retarded by tight metabolic control in patients with type I diabetes mellitus. Seventy-one patients and 115 age-matched healthy control subjects underwent studies of nerve conduction in peroneal and sural nerves. The presence of diabetes was associated with a reduction in peroneal motor nerve conduction velocity (MCV) by 5.9 m/s, sural sensory nerve conduction velocity (SCV) by 3.4 m/s, and sural sensory nerve action potential (SNAP) amplitude by 22%. Dysfunction in peroneal MCV, sural SCV, and sural SNAP were related to long-term poor metabolic control. Eleven of 12 patients with HbA1c <6.5% had normal nerve conduction or abnormality in only one nerve as compared to 2 of 15 patients with HbA1c >8.0%. It is concluded that tight long-term metabolic control (HbA1c <6.5%) can retard nerve dysfunction in patients with type I diabetes mellitus and a mean disease duration of 12 years.

  • 17.
    Jonsdottir, B
    et al.
    Lund University, Sweden .
    Andersson, C
    Lund University, Sweden .
    Carlsson, A
    Lund University, Sweden .
    Delli, A
    Lund University, Sweden .
    Forsander, G
    Karolinska Institute, Sweden .
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Marcus, C
    Karolinska Institute, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Ortqvist, E
    Karolinska Institute, Sweden .
    Lernmark, A
    Lund University, Sweden .
    Ivarsson, S-A
    Lund University, Sweden .
    Elding Larsson, H
    Lund University, Sweden .
    Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 8, p. 1735-1742Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. less thanbrgreater than less thanbrgreater thanBlood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). less thanbrgreater than less thanbrgreater thanAt type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p andlt; 0.0001). GADA was positively associated with TPOAb (p andlt; 0.001) and with TGAb (p andlt; 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p (c)) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p (c) = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. less thanbrgreater than less thanbrgreater thanGADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.

  • 18.
    Jonsdottir, Berglind
    et al.
    Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Sweden.
    Larsson, Christer
    Department of Laboratory Medicine, Lund University, Lund. Sweden.
    Carlsson, Annelie
    Department of Pediatrics, Lund University, Skåne University Hospital, Lund, Sweden.
    Forsander, Gun
    Department of Pediatrics, The Queen Silvia Children´s Hospital, Gothenburg, Sweden.
    Ivarsson, Sten Anders
    Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Sweden.
    Lernmark, Åke
    Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Sweden.
    Ludvigsson, Johnny
    Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping. Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Marcus, Claude
    Division of Pediatrics, Department of Clinical Science, Intervention and Technology Karolinska Institute, Stockholm, 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.
    Örtqvist, Eva
    Pediatric Endocrinology Unit, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
    Elding Larsson, Helena
    Department of Clinical Sciences, Lund University, Skåne University Hospital Malmö, Sweden.
    Thyroid and islet autoantibodies predict autoimmune thyroid disease already at Type 1 diabetes diagnosis.2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 4, p. 1277-1285Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Screening of autoimmune thyroid disease in children and young adults with Type 1 diabetes is important but vary greatly between clinics.

    OBJECTIVE: The aim was to determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA- DQ at diagnosis of Type 1 diabetes for autoimmune thyroid disease during subsequent follow-up.

    SETTING: 43 Paediatric Endocrinology units Sweden. Design, patients and main outcome measures: At diagnosis of Type 1 diabetes, samples from 2433 children were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), and the three variants of the zinc transporter 8 (ZnT8W/R/QA) as well as HLA-DQA1-B1 genotypes and thyroid function. After 5.1-9.5 years disease duration, children treated with thyroxine were identified in the Swedish National Board of Health and Welfare Prescribed Drug Register.

    RESULTS: Thyroxine had been prescribed to 6% (147/2433; 66% girls). In patients below 5 years, female gender (HR=4.60, p=0.008) and GADA (HR=5.80, p=0.02) were significant predictors. In patients 5-10 years, TPOAb (HR=20.56, p<0.0001), TGAb (HR=3.40, p=0.006) and TSH outside the reference limit (HR=3.64, p<0.001) were predictors while in the 10-15 year olds, TPOAb (HR=17.00, p<0.001) and TSH outside the reference limit (HR=4.11, p<0.001) predicted future thyroxine prescription.

    CONCLUSION: In addition to TPOAb and TSH, positive GADA tested at the diagnosis of type 1 diabetes is important for the prediction of autoimmune thyroid disease in children below 5 years of age.

  • 19.
    Lannering, Birgitta
    et al.
    University of Gothenburg.
    Sandstrom, Per-Erik
    Umeå University.
    Holm, Stefan
    Karolinska Institute.
    Lundgren, Johan
    Lund University.
    Pfeifer, Susan
    Uppsala University.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Stromberg, Bo
    Uppsala University.
    Gustafsson, Goran
    Karolinska Institute.
    Classification, incidence and survival analyses of children with CNS tumours diagnosed in Sweden 1984-20052009In: ACTA PAEDIATRICA, ISSN 0803-5253, Vol. 98, no 10, p. 1620-1627Article in journal (Refereed)
    Abstract [en]

    Aim: Primary tumours in the central nervous system (CNS) are the second most common malignancy in childhood after leukaemia. Sweden has a high incidence and a high-survival rate in international comparative studies. This has raised the question about the type of tumours included in the Swedish Cancer registry. We therefore compared international data to the Swedish Childhood Cancer registry. Methods: Central nervous system tumours registered in the Swedish Childhood Cancer Registry were reclassified according to ICCC-3. Incidence and survival analyses were performed in the study population. Results: There were 1479 children (andlt; 15 years) in Sweden diagnosed with CNS tumours 1984-2005. The distribution of diagnoses was similar to that reported in other studies. The annual incidence was 4.2/100 000 children. The survival rates have not improved significantly between the two time periods before/after 1995 (70% vs. 74%; p = 0.10). Conclusions: The mean annual incidence of children with CNS tumours was 4.2/100 000 and has not increased during the study period. Survival rate for brain tumours at 10 years follow-up was 72%.

  • 20.
    Ljungkrantz, M
    et al.
    Dept of Pediatrics Blekingesjukhuset, Karlskrona.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Type 1 diabetes: Increased height and weight gains in early childhood2008In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, no 3 PART 2, p. 50-56Article in journal (Refereed)
    Abstract [en]

    Objective: The accelerator/beta-cell stress hypothesis regards insulin resistance as one common basis for type 1 and type 2 diabetes and weight increase as an important trigger of type 1 diabetes. To test this hypothesis, we examined children's height and weight gain from birth to the time of diagnosis of type 1 diabetes. Method: Growth charts (n=316) from children 0-16yr old up to the time of diagnosis of type 1 diabetes were compared with growth charts from age- and sex-matched controls. Results: Compared with their controls, children who developed diabetes had experienced more pronounced gain in both weight and height. In the year of diagnosis, they were taller [0.5 vs. 0.36 standard deviation score (SDS), p<0.03] and heavier (0.7 vs. 0.45 SDS, p<0.01). Children who developed diabetes aged 5yr or less gained more weight during the period between their third month and third year of life (p<0.01). Children who were diagnosed between 6 and 10yr of age had gained more in height before they were 5yr old (p<0.05). Regression analysis showed that a high weight or a high body mass index (BMI) at 5yr of age indicated, more than the other measurements, a high risk for diabetes later during childhood, while height and weight at ages less than 5yr did not add any further information on diabetes risk. Conclusions: Rapid growth before 7yr of age and increased BMI in childhood are risk factors for later type 1 diabetes. These findings support the accelerator/beta-cell stress hypothesis. © 2008 The Author Journal compilation © 2008 Blackwell Munksgaard.

  • 21.
    Ludvigsson, Johnny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Carlsson, A
    University of Lund Hospital.
    Forsander, G
    Queen Silvia Childrens Hospital.
    Ivarsson, S
    University Hospital MAS.
    Kockume, I
    Karolinska Institute.
    Lernmark, A
    Lund University.
    Lindblad, B
    Queen Silvia Childrens Hospital.
    Marcus, C
    Karolinska University.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    C-peptide in the classification of diabetes in children and adolescents2012In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 13, no 1, p. 45-50Article in journal (Refereed)
    Abstract [en]

    Aim: To report C-peptide results in newly diagnosed patients and the relation to clinical diagnosis of diabetes. less thanbrgreater than less thanbrgreater thanMethods: A nation-wide cohort, the Better Diabetes Diagnosis study was used to determine serum C-peptide at diagnosis in 2734 children and adolescents. Clinical data were collected at diagnosis and follow-up. C-peptide was determined in a validated and controlled time-resolved fluoroimmunoassay. less thanbrgreater than less thanbrgreater thanResults: The clinical classification of diabetes, before any information on human leukocyte antigen, islet autoantibodies, or C-peptide was received, was type 1 diabetes (T1D) in 93%, type 2 diabetes (T2D) in 1.9%, maturity onset diabetes of the young (MODY) in 0.8%, secondary diabetes (0.6%), while 3.3% could not be classified. In a random, non-fasting serum sample at diagnosis, 56% of the patients had a C-peptide value andgt; 0.2 nmol/L. Children classified as T2D had the highest mean C-peptide (1.83 + 1.23 nmol/L) followed by MODY (1.04 +/- 0.71 nmol/L) and T1D (0.28 +/- 0.25 nmol/L). Only 1/1037 children who had C-peptide andlt; 0.2 nmol/L at diagnosis was classified with a type of diabetes other than T1D. Predictive value of C-peptide andgt; 1.0 nmol/L for the classification of either T2D or MODY was 0.46 [confidence interval 0.37-0.58]. less thanbrgreater than less thanbrgreater thanConclusions: More than half of children with newly diagnosed diabetes have clinically important residual beta-cell function. As the clinical diagnosis is not always straightforward, a random C-peptide taken at diagnosis may help to classify diabetes. There is an obvious use for C-peptide determinations to evaluate beta-cell function in children with diabetes.

  • 22.
    Ludvigsson, Johnny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Carlsson, Annelie
    University of Lund Hospital, Sweden .
    Deli, Ahmed
    Lund University, Sweden .
    Forsander, Gun
    Queen Silvia Childrens Hospital, Sweden .
    Ivarsson, Sten-A
    University Hospital MAS, Sweden .
    Kockum, Ingrid
    Karolinska Institute, Sweden .
    Lindblad, Bengt
    Queen Silvia Childrens Hospital, Sweden .
    Marcus, Claude
    Karolinska University Hospital, Sweden .
    Lernmark, Ake
    Lund University, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Decline of C-peptide during the first year after diagnosis of Type 1 diabetes in children and adolescents2013In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 100, no 2, p. 203-209Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: We studied the decline of C-peptide during the first year after diagnosis of Type 1 diabetes (T1D), and its relation to various factors. less thanbrgreater than less thanbrgreater thanMethods: 3824/4017 newly diagnosed patients (95%) were classified as T1D in a national study. In a non-selected subgroup of 1669 T1D patients we determined non-fasting C-peptide both at diagnosis and after 1 year, and analyzed decline in relation to clinical symptoms and signs, initial C-peptide and occurrence of auto-antibodies. less thanbrgreater than less thanbrgreater thanResults: Younger children lost more C-peptide (p andlt; 0.001) and the higher the C-peptide at diagnosis the larger the decline during the first year (p andlt; 0.0000). Patients with higher BMI had higher C-peptide at diagnosis but lost more (p andlt; 0.01), and those with lower HbA1c, without symptoms and signs at diagnosis, and with higher BMI, had higher C-peptide at diagnosis, but lost more during the first year (p andlt; 0.001). Finally, patients diagnosed during autumn had higher C-peptide at diagnosis, but lost more during the coming year (p andlt; 0.001). Occurrence of auto-antibodies did not correlate with C-peptide decline, except possibly for a more rapid loss in IAA-positive patients. less thanbrgreater than less thanbrgreater thanConclusions/interpretation: Even in a restricted geographical area and narrow age range (andlt; 18 years), the natural course of Type 1 diabetes is heterogeneous. This should be considered in clinical trials.

  • 23.
    Ludvigsson, Johnny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Holmqvist, Britt-Marie
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Does modern high standard life style cause type 1 diabetes in children?2013In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 29, no 2, p. 161-165Article in journal (Refereed)
    Abstract [en]

    Background Type 1 diabetes is a serious disease which, in spite of intensive treatment, causes serious complications and increased mortality. The incidence is increasing, but the aetiology is unknown. As part of modern lifestyle, increased hygiene has been suspected as one contributing cause but so far there is no evidence. Several large epidemiological studies, mainly restricted to children with increased genetic risk for type 1 diabetes, have so far given no clue. Methods All Babies in Southeast Sweden is unique in its design as it has followed an unselected group of children from birth 19971999 and onwards with regular follow-ups. This report is based on questionnaires from initially 16051 children of whom 80 have later on developed type 1 diabetes. The parents answered questionnaires at the birth of their child and then after 1, 23, 56 and 8years. A number of parameters possibly related to hygiene were analysed with several statistical methods, both with univariate and in regression models. Results Our study cannot identify any crucial environmental factor. This indicates that hygiene-related parameters traditionally regarded as part of modern life style do not play any important role for the aetiology of type 1 diabetes. Conclusions There is no reason to recommend a change of that part of our lifestyle. We find weak associations to previous gastrointestinal infections, which gives a hint that development of type 1 diabetes may be related to problems in the gut and maybe one should look closer into the microbes living in the gut.

  • 24.
    Ludvigsson, Johnny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Krisky, David
    Diamyd Medical, Pittsburgh.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Battelino, Tadej
    University Medical Center–University Children's Hospital, Faculty of Medicine, Ljubljana, Slovenia .
    Castaño, Luis
    Hospital de Cruces–University of Basque Country, Barakaldo, Bizkaia, Spain .
    Greening, James
    Department of Paediatrics, Leicester Royal Infirmary, Leicester, UK.
    Kordonouri, Olga
    Diabetes Center for Children and Adolescents, Kinderkrankenhaus auf der Bult, Hannover, Germany .
    Otonkoski, Timo
    Children's Hospital, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland.
    Pozzilli, Paolo
    University Campus Bio-Medico, Rome, Italy.
    Robert, Jean-Jacques
    Hôpital Necker–Enfants Malades, Université René Descartes Paris 5, Paris, France.
    Veeze, Henk J.
    Stichting Diabeter, Rotterdam, the Netherlands .
    Palmer, Jerry
    Department of Medicine, Veterans Affairs Puget Sound Health Care System and University of Washington, Seattle, USA.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Elding Larsson, Helena
    Lunds universitet, Sweden.
    Åman, Jan
    Örebro universitet, Sweden.
    Kärdell, Gunilla
    Neiderud, Jan
    Helsingborgs lasarett, Sweden.
    Lundström, Göran
    Länssjukhuset Kalmar, Sweden.
    Albinsson, Eva
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Carlsson, Annelie
    Skånes universitetssjukhus, Lund, Sweden.
    Nordvall, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Norrköping.
    Fors, Hans
    Sahlgrenska akademin vid Göteborgs universitet, Sweden.
    Arvidsson, Carl-Göran
    Centrallasarettet, Västerås, Sweden.
    Edvardson, Stig
    Centrallasarettet, Växjö, Sweden.
    Hanås, Ragnar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Larsson, Karin
    Rathsman, Björn
    Sachsska Barnsjukhuset, Stockholm, Sweden.
    Forsgren, Henrik
    Desaix, Helena
    Forsander, Gun
    Göteborg University, Sweden.
    Nilsson, Nils-Östen
    Lasarettet i Halmstad, Sweden.
    Åkesson, Carl-Göran
    Keskinen, Päivi
    University of Tampere, Finland .
    Veijola, Riitta
    Uleåborgs universitetssjukhus, Finland.
    Talvitie, Timo
    Raile, Klemens
    Charite, Berlin, Germany.
    Kapellen, Thomas
    University of Leipzig, Germany.
    Burger, Walter
    Neu, Andreas
    University Children's Hospital, Tuebingen, Germany.
    Engelsberger, Ilse
    Heidtmann, Bettina
    Catholic Children’s Hospital Wilhelmstift, Hamburg, Germany.
    Bechtold, Suzanne
    Leslie, David
    Blizard Institute, Queen Mary University of London, UK.
    Chiarelli, Francesco
    University of Chieti, Italy.
    Cicognani, Alesandro
    University of Bologna, Italy.
    Chiumello, Giuseppe
    Vita-Salute University, Milan, Italy.
    Cerutti, Franco
    University of Turin, Italy.
    Zuccotti, Gian Vincenzo
    University of Milan, Italy.
    Gomez Gila, Ana
    Rica, Itxaso
    Barrio, Raquel
    Clemente, Maria
    López Garcia, Maria José
    Rodriguez, Mercedes
    Gonzalez, Isabel
    Lopez, Juan Pedro
    Oyarzabal, Mirentxu
    Reeser, H M
    Nuboer, Roos
    Stouthart, Pauline
    Bratina, Natasa
    Bratanic, Nina
    de Kerdanet, Marc
    Weill, Jacques
    Ser, Nicole
    Barat, Pascal
    Bertrand, Anne Marie
    Carel, Jean-Claude
    Reynaud, Rachel
    Coutant, Regis
    Baron, Sabine
    GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus2012In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 366, no 5, p. 433-442Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The 65-kD isoform of glutamic acid decarboxylase (GAD65) is a major autoantigen in type 1 diabetes. We hypothesized that alum-formulated GAD65 (GAD-alum) can preserve beta-cell function in patients with recent-onset type 1 diabetes.

    METHODS: We studied 334 patients, 10 to 20 years of age, with type 1 diabetes, fasting C-peptide levels of more than 0.3 ng per milliliter (0.1 nmol per liter), and detectable serum GAD65 autoantibodies. Within 3 months after diagnosis, patients were randomly assigned to receive one of three study treatments: four doses of GAD-alum, two doses of GAD-alum followed by two doses of placebo, or four doses of placebo. The primary outcome was the change in the stimulated serum C-peptide level (after a mixed-meal tolerance test) between the baseline visit and the 15-month visit. Secondary outcomes included the glycated hemoglobin level, mean daily insulin dose, rate of hypoglycemia, and fasting and maximum stimulated C-peptide levels.

    RESULTS: The stimulated C-peptide level declined to a similar degree in all study groups, and the primary outcome at 15 months did not differ significantly between the combined active-drug groups and the placebo group (P=0.10). The use of GAD-alum as compared with placebo did not affect the insulin dose, glycated hemoglobin level, or hypoglycemia rate. Adverse events were infrequent and mild in the three groups, with no significant differences.

    CONCLUSIONS: Treatment with GAD-alum did not significantly reduce the loss of stimulated C peptide or improve clinical outcomes over a 15-month period.

  • 25.
    Ludvigsson, Johnny
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Samuelsson, Ulf
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Continuous insulin infusion (CSII) or modern type of multiple daily injections (MDI) in diabetic children and adolescents a critical review on a controversial issue2007In: Pediatric Endocrinology Reviews: diabetes, nutrition, metabolism, ISSN 1565-4753, Vol. 5, no 2, p. 666-678Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    There is a common opinion that CSII is superior to MDI. CSII offers the most physiological insulin substitution.

    METHOD:

    Review of recent publications (Cochrane criteria), on modern multiple daily injections (MDI) based on insulin analogues, modern self-control and education.

    RESULTS:

    There is a lack of randomised controlled studies comparing CSII with modern MDI in children and adolescents. In some studies CSII seems to give a slight decrease of HbA1c, a slightly better quality of life, perhaps less hypoglycemia. However, serious hypoglycemia, sometimes fatal, occurs, DKA seems to increase, weight gain and local infections at injection sites may occur and CSII is more expensive than MDI.

    CONCLUSION:

    CSII is a useful tool. It is reasonable to use it when there are appropriate indications. CSII does not solve all problems but has to be combined with other important parts of diabetes treatment.

  • 26.
    Ludvigsson, Johnny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Johansson, C
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Berlin, Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Transfusion Medicine. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Photopheresis at onset of type 1 diabetes: A randomised, double blind, placebo controlled trial2001In: Archives of Disease in Childhood, ISSN 0003-9888, E-ISSN 1468-2044, Vol. 85, no 2, p. 149-154Article in journal (Refereed)
    Abstract [en]

    Background - In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. Aim - To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. Methods - A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included, 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). Results - The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group, there was no difference between the groups regarding HbAlc values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. Conclusion - Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.

  • 27.
    Ludvigsson, Johnny
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Johansson, C
    Stenhammar, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Treatment with antioxidants at onset of type 1 diabetes in children: a randomized, double-blind placebo-controlled study.2001In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 17, p. 131-136Article in journal (Refereed)
  • 28.
    Nordfeldt, Sam
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Child and Adolescent Psychiatry. Östergötlands Läns Landsting, CPS - Centrum för psykiatri och samhällsmedicin, BUP - Barn- och ungdomspsykiatri.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Serum ACE predicts severe hypoglycemia in children and adolescents with type 1 diabetes2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 2, p. 274-278Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE - To investigate whether risk of severe hypoglycemia is related to serum (S) ACE level during intensive treatment in type 1 diabetic children. RESEARCH DESIGN AND METHODS - A cohort of 86 intensively treated type 1 diabetic patients was studied during 1999-2000. In 1999, the age range was 7-19 years (median 12.8), diabetes duration was 1.2-14.7 years (5.3), insulin dose was 0,4-1.7 units ╖ kg-1 ╖ 24 h-1 (1.0), and the HbA1c year mean was 4.7-10.2% (6.8). HbA1c, insulin doses, and events of severe hypoglycemia (needing assistance from another person) were prospectively registered at regular visits, scheduled quarterly. S-ACE was determined once. RESULTS - Severe hypoglycemia was correlated to S-ACE (r = 0.22, 95% CI 0.0I-0.41, P = 0.0093). The square root of severe hypoglycemia was correlated to S-ACE (r = 0.27, 95% CI 0.06-0.45, P = 0.0093). Patients with S-ACE at the median level or above (n = 44) reported a mean of 3.0 yearly events of severe hypoglycemia compared with 0.5 events in patients with S-ACE lower than the median (n = 42) (P = 0.0079). Of the patients with an S-ACE at the median level or above, 27 (61%) reported severe hypoglycemia, compared with 17 (40%) patients with an S-ACE lower than the median (P = 0.0527). Insulin dose, HbA1c, age, onset age, duration, C-peptide, and sex did not differ between these two groups. S-ACE was negatively correlated with age (r = -0.27, 95% CI -0.46 to 0.07, P = 0.0265) but not with HbA1c, duration, or blood pressure. CONCLUSIONS - The elevated rate of severe hypoglycemia among patients with higher S-ACE suggests, among other factors, that a genetic determinant for severe hypoglycemia exists. Further evaluation is needed before the clinical usefulness of this test can be elucidated.

  • 29.
    Panagopoulos, Ioannis
    et al.
    Dept of Clin Genetics Lund.
    Fioretos, Thoas
    Dept of Clin Genetics, Lund.
    Isaksson, Margareth
    Dept of Clin Genetics, Lund.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Billström, Rolf
    Dept of Internal Medicine Lund.
    Strömbeck, Bodil
    Dept of Clinical Genetics, Lund.
    Mitelman, Felix
    Dept of Clin Genetics Lund.
    Johansson, Bertil
    Dept of Clin Genetics, Lund.
    Fusion of the MORF and CBP genes in acute myeloid leukemia with the t(10,16)(q22,p13)2001In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 10, no 4, p. 395-404Article in journal (Refereed)
    Abstract [en]

    The CBP gene at 16p 13 fuses to MOZ and MLL as a result of the t(8,16)(p11,p13) in acute (myelo)monocytic leukemias (AML M4/M5) and the t(11,16)(q23,p13) in treatment-related AML, respectively. We show here that a novel t(10,16)(q22,p13) in a childhood AML M5a leads to a MORF-CBP chimera. RT-PCR using MORF forward and CBP reverse primers amplified a MORF-CBP fusion in which nucleotide 3103 of MORF was fused in-frame with nucleotide 284 of CBP. Nested RT-PCR with CBP forward and MORF reverse primers generated a CBP-MORF transcript in which nucleotide 283 of CBP was fused in-frame with nucleotide 3104 of MORF. Genomic analyses revealed that the breaks were close to Alu elements in intron 16 of MORF and intron 2 of CBP and that duplications had occurred near the breakpoints. A database search using MORF cDNA enabled us to construct an exon-intron map of the MORF gene. The MORF-CBP protein retains the zinc fingers, two nuclear localization signals, the histone acetyltransferase (HAT) domain, a portion of the acidic domain of MORF and the CBP protein downstream of codon 29. Thus, the part of CBP encoding the RARA-binding domain, the CREB-binding domain, the three Cys/His-rich regions, the bromodomain, the HAT domain and the Glu-rich domains is present. In the reciprocal CBP-MORF, part of the acidic domain and the C-terminal Ser- and Met-rich regions of MORF are likely to be driven by the CBP promoter. Since both fusion transcripts were present, their exact role in the leukemogenic process remains to be elucidated.

  • 30.
    Peterson, Anette
    et al.
    Jonköping University, Sweden Jonköping County Council, Sweden .
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Akesson, Karin
    County Hospital Ryhov, Sweden Jonköping University, Sweden Jonköping County Council, Sweden .
    Bojestig, Mats
    Jonköping University, Sweden Jonköping County Council, Sweden .
    Andersson Gare, Boel
    Jonköping University, Sweden Jonköping County Council, Sweden .
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Improved Results in Paediatric Diabetes Care Using a Quality Registry in an Improvement Collaborative: A Case Study in Sweden2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, p. e0097875-Article in journal (Refereed)
    Abstract [en]

    Background: Several studies show that good metabolic control is important for children and adolescents with type 1 diabetes. In Sweden, there are large differences in mean haemoglobin A1c (HbA1c) in different hospitals and difficulties implementing national guidelines in everyday practice. This study shows how the participation in an improvement collaborative could facilitate improvements in the quality of care by paediatric diabetes teams. The Swedish paediatric diabetes quality registry, SWEDIABKIDS was used as a tool and resource for feedback and outcome measures. Methods: Twelve teams at paediatric diabetes centres, caring for 30% (2302/7660) of patients in Sweden, participated in an 18-month quality improvement program. Each team defined treatment targets, areas needing improvement, and action plans. The main outcome was the centre patients mean HbA1c levels, but other clinical variables and change concepts were also studied. Data from the previous six months were compared with the first six months after starting the program, and the long-term follow up after another eleven months. Results: All centres reduced mean HbA1c during the second and third periods compared with the first. The mean reduction for all was 3.7 mmol/mol (pless than0.001), compared with non-participating centres who improved their mean HbA1c with 1.7 mmol/mol during the same period. Many of the participating centres reduced the frequency of severe hypoglycaemia and/or ketoacidosis, and five centres reached their goal of ensuring that all patients had some sort of physical activity at least once weekly. Change concepts were, for example, improved guidelines, appointment planning, informing the patients, improving teamwork and active use of the registry, and health promotion activities. Conclusions: By involving paediatric diabetes teams in a quality improvement collaborative together with access to a quality register, the quality of paediatric diabetes care can improve, thereby contributing to a reduced risk of late complications for children and adolescents with diabetes.

  • 31.
    Petersson, Christina
    et al.
    Jonköping University, Sweden.
    Huus, Karina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Samuelsson, Ulf
    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.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Akesson, Karin
    Ryhov Hospital Jonköping, Sweden.
    Use of the national quality registry to monitor health-related quality of life of children with type I diabetes: A pilot study2015In: Journal of Child Health Care, ISSN 1367-4935, E-ISSN 1741-2889, Vol. 19, no 1, p. 30-42Article in journal (Refereed)
    Abstract [en]

    The management of diabetes is complicated, as treatment affects the everyday life of both children and their families. To enable optimal care for children with type I diabetes, it is important to highlight health-related quality of life (HrQoL) as well as medical outcomes to detect psychological problems that otherwise could be missed. The aim was to study HrQoL in children and adolescents with type I diabetes dependent on gender, age and co-morbidity and to study the consistency between childrens self-reporting and parents proxy reporting. The cross-sectional data were collected using the questionnaire DISABKIDS Chronic Generic Measure and the DISABKIDS diabetes module. Parents in the proxy report perceived their childrens HrQoL to be lower than children themselves. Boys reported their HrQoL to be better than girls. Results show that living with an additional disease has an impact on the HrQoL, which is an important factor to consider in the quality registry. Assessing HrQoL on a routine basis may facilitate detection and discussion of HrQoL-related questions in the national quality registry.

  • 32.
    Ping Zhao, Lue
    et al.
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Alshiekh, Shehab
    Lund University, Sweden.
    Zhao, Michael
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Carlsson, Annelie
    Lund University, Sweden.
    Elding Larsson, Helena
    Lund University, Sweden.
    Forsander, Gun
    Sahlgrens University Hospital, Sweden.
    Ivarsson, Sten A.
    Lund University, Sweden.
    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.
    Kockum, Ingrid
    Karolinska Institute, Sweden.
    Marcus, Claude
    Karolinska Institute, Sweden.
    Persson, Martina
    Karolinska Institute, Sweden.
    Samuelsson, Ulf
    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.
    Ortqvist, Eva
    Karolinska Institute, Sweden.
    Pyo, Chul-Woo
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Nelson, Wyatt C.
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Geraghty, Daniel E.
    Fred Hutchinson Cancer Research Centre, WA 98104 USA.
    Lernmark, Ake
    Lund University, Sweden.
    Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 3, p. 710-718Article in journal (Refereed)
    Abstract [en]

    The possible contribution of HLA-DRB3, -DRB4, and -DRB5 alleles to type 1 diabetes risk and to insulin autoantibody (IAA), GAD65 (GAD autoantibody [GADA]), IA-2 antigen (IA-2A), or ZnT8 against either of the three amino acid variants R, W, or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next-generation sequencing (NGS) was used to determine all DRB alleles in consecutively diagnosed patients ages 1-18 years with islet autoantibody-positive type 1 diabetes (n = 970) and control subjects (n = 448). DRB3, DRB4, or DRB5 alleles were tested for an association with the risk of DRB1 for autoantibodies, type 1 diabetes, or both. The association between type 1 diabetes and DRB1*03:01:01 was affected by DRB3*01:01:02 and DRB3*02:02:01. These DRB3 alleles were associated positively with GADA but negatively with ZnT8WA, IA-2A, and IAA. The negative association between type 1 diabetes and DRB1*13:01:01 was affected by DRB3*01:01:02 to increase the risk and by DRB3*02:02:01 to maintain a negative association. DRB4*01:03:01 was strongly associated with type 1 diabetes (P = 10(-36)), yet its association was extensively affected by DRB1 alleles from protective (DRB1*04:03:01) to high (DRB1*04:01:01) risk, but its association with DRB1*04:05:01 decreased the risk. HLA-DRB3, -DRB4, and -DRB5 affect type 1 diabetes risk and islet autoantibodies. HLA typing with NGS should prove useful to select participants for prevention or intervention trials.

  • 33.
    Priftakis, Peter
    et al.
    Karolinska institutet.
    Dalianis, Tina
    Karolinska institutet.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Oncology Centre.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lewensohn-Fuchs, Ilona
    Karolinska institutet.
    Bogdanovic, Gordana
    Karolinska institutet.
    Winiarski, Jacek
    Karolinska institutet.
    Gustafsson, Britt
    Karolinska institutet.
    Human polyomavirus DNA is not detected in Guthrie cards (dried blood spots) from children who developed acute lymphoblastic leukemia2003In: Medical and Pediatric Oncology, ISSN 0098-1532, E-ISSN 1096-911X, Vol. 40, no 4, p. 219-223Article in journal (Refereed)
    Abstract [en]

    Background

    Epidemiological evidence has suggested that some childhood acute lymphoblastic leukemia (ALL) may be initiated in utero and may have an infectious etiology. The human polyomavirus JC virus (JCV) has been discussed as a candidate virus, but its presence has not been demonstrated in leukemia cells from children with ALL. The aim of this study was, therefore, to investigate if prenatal human polyomavirus infection could still indirectly be correlated to the development of childhood ALL.

    Procedure

    Fifty-four Guthrie cards (stored, dried blood spots filter papers, routinely collected from newborns for different screening analyses), collected at 3–5 days of age, from Swedish children who subsequently developed ALL, as well as from 37 healthy controls, were investigated by nested PCR for the presence of human polyomaviruses JCV and BK virus (BKV).

    Results

    JCV and BKV DNA were not detected in any of the Guthrie cards from ALL patients or from healthy controls, although all tested samples had amplifiable DNA as confirmed by an HLA DQ PCR.

    Conclusions

    JCV or BKV were not found in any of the dried blood spots of children who later developed ALL or in the healthy controls. These findings suggest that it is unlikely that childhood ALL is associated with an in utero infection with JCV or BKV, although it is not possible to exclude an association with an in utero infection that has become latent in the kidneys with very low levels of circulating virus at birth.

  • 34.
    Sadauskaite-Kühne, Vaiva
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Padaiga, Zilvinas
    Laboratory of Paediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Jasinskiene, Edita
    Laboratory of Paediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Samuelsson, Ulf
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Longer breastfeeding is an independent protective factor against development of type 1 diabetes mellitus in childhood2004In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 20, no 2, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Background

    Early weaning diet, early introduction of breast milk substitution and cow's milk have been shown to increase the risk of type 1 diabetes later in life. It is also shown that older maternal age, maternal education, preeclampsia, prematurity, neonatal illness and neonatal icterus caused by blood group incompatibility, infections and stress might be risk factors for type 1 diabetes. We aimed to determine whether early nutrition is an independent risk factor for diabetes despite other life events.

    Methods

    Data from 517 children (268 boys and 249 girls) in south-east of Sweden and 286 children (133 boys and 153 girls) in Lithuania in the age group of 0 to 15 years with newly diagnosed type 1 diabetes mellitus were included into analysis. Three age- and sex-matched healthy controls were randomly selected. Response rate in control families in Sweden was 72.9% and in Lithuania 94.8%. Information was collected via questionnaires.

    Results

    Exclusive breastfeeding longer than five months (odds ratio 0.54, 95% confidence interval 0.36–0.81) and total breastfeeding longer than 7 (0.56, 0.38–0.84) or 9 months (0.61, 0.38–0.84), breastfeeding substitution that started later than the third month (0.57, 0.33–0.98) among Swedish children 5 to 9 years old and later than the seventh month (0.24, 0.07–0.84) among all Swedish children is protective against diabetes when adjusted for all other above-listed risk factors. In Lithuania, exclusive breastfeeding longer than two months in the age group of 5 to 9 years is protective (0.58, 0.34–0.99) when adjusted for other factors.

    Conclusions

    Longer exclusive and total breastfeeding appears as an independent protective factor against type 1 diabetes.

  • 35.
    Saduaskaite-Kühne, Vaiva
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Zilvinas, Padaiga
    Department of Preventive Medicine, Kaunas University of Medicine, Kaunas, Lithuania.
    Samuelsson, Ulf
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Stress and social factors in relation to risk for type 1 diabetesManuscript (preprint) (Other academic)
    Abstract [en]

    Background. Previous studies have shown controversial results regmding conelation between social status and risk for Type 1 diabetes mellitus (DM). Stress and infections have been shown to increase risk for Type 1 DM. We looked upon these factors in relation to risk for Type 1 DM in two countries, where incidence of the disease is very different.

    Methods. Data from 0-15 years old 517 children (268 boys and 249 girls) in South-East of Sweden and 286 children (133 boys and 153 girls) in Lithuania with newly diagnosed type 1 diabetes mellitus were included into analysis. Three age and sex matched healthy controls were randomly selected. Response rate in control families in Sweden was 72.9% and in Lithuania 94.8%. Information was collected via questionnaires.

    Results. Psychosocial stress and infections were risk factors for developing Type 1 DM in both countries (in Sweden OR 1.34, CI 1.01-1.79 and 1.99, CI 1.61-2.46 respectively, and in Lithuania 2.29, CI 1.59-3.32 and 1.82, CI 1.36-2.43, respectively). High social mixing of the mothers was also increasing risk for diabetes for the children in both countries (OR 1.32, CI 1.03-1.70 in Sweden and 1.45, CI 1.03-2.04 in Lithuania). Mother's age over 30 years at birth was a protective factor in Sweden (OR 0.66, CI 0.53-0.84), whereas in Lithuania it was a risk factor (OR 1.53, CI 1.14-2.06).

    Conclusious. Psychosocial stress and infections are uniform risk factors, despite the various rate of incidence in the country. Other factors have more complex influence on the risk for diabetes.

  • 36.
    Saduaskaite-Kühne, Vaiva
    et al.
    Laboratory of Paediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Samuelsson, Ulf
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Jasinskiene, E.
    Laboratory of Paediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Padaiga, Zilvinas
    Laboratory of Paediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Urbonaite, B.
    Laboratory of Paediatric Endocrinology, Kaunas University of Medicine, Kaunas, Lithuania.
    Edenvall, Hans
    Department of Paediatrics, Central Hospital, Karlskrona, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Severity at onset of childhood type 1 diabetes in countries with high and low incidence of the condition2002In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 55, no 3, p. 247-254Article in journal (Refereed)
    Abstract [en]

    Severity of Type 1 diabetes mellitus (DM) at presentation was compared between south-east Sweden and Lithuania where incidence of childhood Type 1 diabetes is three times lower than in Sweden. New cases of diabetes at age 0–15 years from August 1995 to March 1999 in south-east Sweden and from August 1996 to August 2000 in Lithuania were included. Symptoms and clinical characteristics at diagnosis were recorded. Data about the close environment were collected using questionnaires. Lithuanian children were diagnosed in a more severe condition, mean pH 7.30 and HbA1c 11.5% compared with mean pH 7.36 and HbA1c 9.7% in Swedish children (P<0.0001). More Lithuanian than Swedish children were diagnosed in ketoacidosis (pH≤7.2, hyperglycaemia and ketonuria), 21.3 versus 7.3% (P<0.0001). Only 4.6% of Swedish children and 1.0% of Lithuanian children had no symptoms (P=0.007). Children in families with at least one first degree relative with diabetes (12.2% in Sweden and 8.4% in Lithuania, NS) had laboratory values at diagnosis closer to normal than sporadic cases in either country. Factors predicting ketoacidosis in Sweden were an unemployed mother and absence of infections in the 6 months before diagnosis. In Lithuania it was younger age and mother with less education. Additional educational activities for doctors are needed in countries with low incidence to reduce prevalence of ketoacidosis at onset.

  • 37. Samuelsson, Andreas
    et al.
    Franzén, Iris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Samuelsson, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Barn och ungdomar med insulinpumpsbehandlad typ 1-diabetes. Bättre metabol kontroll kan uppnås. Aktiv utbildning och tät kontakt krävs.2002In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 99, p. 1051-1055Article in journal (Other academic)
  • 38.
    Samuelsson, Ulf
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Why do children get diabetes?: A study on some genetical, immunological and environmental factors1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Insulin dependent diabetes mellitus (IDDM) is one of the most common and serious chronic disorders of childhood. Despite advances in the knowledge about the cause of IDDM during the last decades the etiology still remains incompletely understood but is probably due to a complex network of genetic, immunological and environmental factors. The aim of the thesis was to elucidate some parts of this network and, if possible, identify riskfactors or markers for the development of IDDM in childhood.

    Background infonnation was received from questionnaires and/or medical records. Islet cell surface antibodies (ICSA) were analysed by a new radioimmunologic method with a specificity of 100 % and a sensitivity of 70 % for positive titers, while the other autoantibodies and C-peptide values were determined by wellknown and accepted methods.

    An international study on 745 HLA-typed children with diabetes indicated that IDDM is genetically heterogenous. Patients with HLA-DR3/nonDR4 generally have a milder form of diabetes than patients without this marker.

    Studies from the South-east region of Sweden showed that early weight gain seems to be more correlated to development of IDDM than breastfeeding resp. non-breastfeeding.

    Analysis of space-time clustering in all cases of childhood diabetes (n=584) diagnosed between 1977-1990 indicates clustering with maximal effect within 7 months and 15 km. The frequency of islet cell antibodies (!CA) among non-diabetic schoolchildren was 1,4 %. Corresponding figures for insulinautoantibodies) IAA) and ICSA were 4,0 % and 4,3 %respectively. Only !CA showed a relationship to C-peptide values. Children with low levels of ICA had high values and vice versa.

    An international family study showed that certain factors seem to cause not only a high incidence of diabetes in Finland and Sweden but also a more aggressive early disease process. ICSA was the only  autoantibody which showed simultaneous positivity in all family members. ICSA had also a similar seasonality as incidence of IDDM and was most common in family members of patients with a short duration of symptoms before diagnosis (<8 days).

    In conclusion, early feeding may be of importance for future development of Type I diabetes not only because of degree of exposition to cow milk proteins but also because of effects on energy intake and early betacellstimulation. Environmental factors, probably infections, are of importance for eliciting the disease. High incidence areas have a moreaggressive disease process than areas with lower incidence. Although signs on an autoimmune attack on the beta cells are rather common in the general population such an attack seldom leads to IDDM. ICSA, contrary to ICA, may reflect an early ongoing disease process in genetically predisposed individuals.

  • 39.
    Samuelsson, Ulf
    et al.
    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.
    Anderzen, Johan
    Ryhov County Hospital, Sweden.
    Gudbjornsdottir, Soffia
    University of Gothenburg, Sweden.
    Steineck, Isabelle
    Copenhagen University Hospital, Denmark.
    Akesson, Karin
    Ryhov County Hospital, Sweden; Jonköping County Council, Sweden.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Teenage girls with type 1 diabetes have poorer metabolic control than boys and face more complications in early adulthood2016In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 30, no 5, p. 917-922Article in journal (Refereed)
    Abstract [en]

    Aims: To compare metabolic control between males and females with type 1 diabetes during adolescence and as young adults, and relate it to microvascular complications. Methods: Data concerning 4000 adolescents with type 1 diabetes registered in the Swedish paediatric diabetes quality registry, and above the age of 18 years in the Swedish National Diabetes Registry was used. Results: When dividing HbA1c values in three groups; amp;lt; 7.4% (57 mmol/mol), 7.4-93% (57-78 mmol/mol) and amp;gt;9.3% (78 mmol/mol), there was a higher proportion of females in the highest group during adolescence. In the group with the highest HbA1c values during adolescence and as adults, 51.7% were females, expected value 46.2%; in the group with low HbA1c values in both registries, 34.2% were females, p amp;lt; 0.001. As adults, more females had retinopathy, p amp;lt; 0.05. Females had higher mean HbAlc values at diagnosis, 112 vs. 10.9% (99 vs. 96 mmol/mol), p amp;lt; 0.03, during adolescence, 8.5 vs. 82% (69 vs. 66 mmol/mol) p amp;lt; 0.01, but not as young adults. Conclusions: Worse glycaemic control was found in adolescent females, and they had a higher frequency of microvascular complications. Improved paediatric diabetes care is of great importance for increasing the likelihood of lower mortality and morbidity later in life. (C) 2016 Elsevier Inc. All rights reserved.

  • 40.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Space-time clustering at birth and at diagnosis of type 1 diabetes mellitus in relation to early clinical manifestation2003In: Journal of Pediatric Endocrinology & Metabolism (JPEM), ISSN 0334-018X, E-ISSN 2191-0251, Vol. 16, no 6, p. 859-867Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate whether space-time clustering at diagnosis of type 1 diabetes mellitus (DM1) is related to clinical manifestations and to see whether there is a time-space clustering at birth of children who later develop DM1. Patients: Using the method by Knox, clustering was analysed in all 1,144 children diagnosed between 1977 and 1994 in south-east Sweden. Results: The strongest significance was obtained for the cut-off value of 5 kin and 7 months (p <0.01). Using this cut-off, children with a short duration of symptoms before diagnosis had the same degree of clustering as children with a longer duration. Children diagnosed during autumn and winter tended to have a higher degree of clustering than children diagnosed during spring and summer. We found no significant clustering regarding birthplace and birth month. Conclusion: This study is consistent with the existence of space-time clustering at diagnosis. The most plausible explanation is that infections elicit several cases of DM1 in children in whom the disease process has already begun.

  • 41.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Division of Health and Society. Linköping University, Faculty of Health Sciences.
    Löfman, Owe
    Östergötlands Läns Landsting, Centre for Public Health Sciences, Centre for Public Health Sciences. Linköping University, Faculty of Health Sciences.
    Nordfeldt, Sam
    Linköping University, Department of Molecular and Clinical Medicine, Child and Adolescent Psychiatry. Linköping University, Faculty of Health Sciences.
    Seasonal variation in the diagnosis of type 1 diabetes in south-east Sweden2007In: Diabetes Research and Clinical Practice, ISSN 0168-8227, E-ISSN 1872-8227, Vol. 76, no 1, p. 75-81Article in journal (Refereed)
    Abstract [en]

    With the aim to survey the seasonal pattern of diagnosis of type 1 diabetes we included all 1903 children <16 years of age and who had been diagnosed with type 1 diabetes between 1977 and 2001 in the south-east of Sweden. To investigate the seasonal pattern a mixture of two cosine functions was included in a logistic regression model.

    There was a clear seasonal variation over the years (p < 0.001). Children in the oldest age group (11–15 years) showed the most obvious seasonal variation (p < 0.001). Children with a short duration of symptoms had about the same seasonal variation as children with a long duration. Both children with and without an infection 3 months prior to diagnosis showed significant seasonal variation (p < 0.001) although the seasonal pattern differed between the two groups (p < 0.001). As the incidence of diabetes increased during the 25 years the study period was divided into periods of 5 years and it was only during the two last periods that significant seasonal variation occurred.

    There is a clear seasonal variation in diagnosis of type 1 diagnosis in children and the results suggest that children with a less aggressive disease process at diagnosis were most responsible for this variation. Children with and without prior infection showed a different seasonal pattern.

  • 42.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Gustafsson, Britt
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Increased prevalence of malignant diseases in the close neighborhood of children with cancer2001In: Journal of environmental health, ISSN 0022-0892, Vol. 64, no 7, p. 18-22Article in journal (Refereed)
    Abstract [en]

    Clustering of cancer in families may be due to chance, inherited genetic mutations, common exposure to environmental agents, or a combination of these factors. The authors, to address a clinical impression that cancer occurs more often in the environment of a child with cancer, investigated whether the prevalence of cancer among children and adults in the neighborhood of children with cancer was higher than the prevalence in the neighborhood of healthy children. One hundred thirty-seven children diagnosed with a malignant disease between 1981 and 1992 at the Department of Pediatrics, University Hospital of Link÷ping, Sweden, were investigated and compared with 232 healthy control children. The control children were traced from the official Swedish population registry. It was found that 13 percent of the children with cancer and six percent of the control children were dose neighbors of other children diagnosed with cancer (p < .05). Cancer also was more common in the circles of acquaintances around the children with cancer than in circles of acquaintances around control children (p < .03). The frequency of cancer in the neighborhood or in the circle of acquaintances was significantly greater in older children than in younger children. These results support the hypothesis that environmental factors can initiate or precipitate cancer in children as well as in adults.

  • 43.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hanås, Ragnar
    Barnkliniken NÄL, Uddevalla.
    Whiss, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Pharmacology .
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Pediatrics . Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Do high blood glucose peaks contribute to higher HbA1c? Results from repeated continuous glucose measurements in children2008In: World Journal of Pediatrics, ISSN 1708-8569, Vol. 4, no 3, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Background: HbA1c levels are infl uenced by the glycemic control of previous 2-3 months. Sometimes patients have surprisingly low HbA1c in spite of many correctly measured high blood glucose values, which is diffi cult to explain. As glucose sensors give an objective picture based on glucose readings several times per minute over 24 hours, we used the area under the curve (AUC) of such subcutaneous glucose profi les to evaluate their relationship with HbA1c. Methods: Thirty-two patients were randomized into two study arms, one open and the other blinded. Both arms had 8 pump users and 8 patients with multiple daily injections (MDI). After three months the two arms crossed over. Both study arms wore a continuous glucose monitoring system (CGMS) for 3 days every 2 weeks. HbA1c was determined before and after each 3-month study period. Results: There was no relationship between HbA1c and s.c. glucose AUC or between HbA1c and the number of peaks >15.0 mmol/L when all CGMS profi les during the 6 months were taken together. Children on MDI showed a positive relationship between HbA1c and AUC (P<0.01) as well as the number of peaks (P<0.01). Children with a negative relationship between HbA1c and AUC generally had fewer fluctuations in blood glucose values, whereas children with a positive relationship had wide fluctuations. Conclusions: Although there was no relationship between s.c. glucose AUC and HbA1c, the results indicate that wide blood glucose fluctuations may be related to high HbA1c values. Therefore, complications and therapeutic interventions should aim at reducing such fluctuations. © Springer 2008.

  • 44.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Johansson, C
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Month of birth and risk of developing insulin dependent diabetes in south east Sweden.  1999In: Archives of Disease in Childhood, ISSN 0003-9888, E-ISSN 1468-2044, Vol. 81, p. 143-146Article in journal (Refereed)
  • 45.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Lindblad, B
    Queen Silvia Children's Hospital, Sweden.
    Carlsson, A
    Lund University Hospital, Sweden.
    Forsander, G
    Queen Silvia Children's Hospital, Sweden.
    Ivarsson, S
    University Hospital MAS, Sweden.
    Kockum, I
    Karolinska Institute, Sweden.
    Lernmark, A
    Lund University, Sweden.
    Marcus, C
    Karolinska University Hospital, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Residual beta cell function at diagnosis of type 1 diabetes in children and adolescents varies with gender and season2013In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 29, no 1, p. 85-89Article in journal (Refereed)
    Abstract [en]

    Background

    There are seasonal variations and gender differences in incidence of type 1 diabetes (T1D), metabolic control and responses to immune interventions at onset of the disease.

    We hypothesized that there are seasonal and gender differences in residual insulin secretion already at diagnosis of T1D.

    Methods

    In 2005, a national study, the Better Diabetes Diagnosis, was started to classify all newly diagnosed children and adolescents with diabetes. About 95% (3824/4017) of the patients were classified as T1D, and our analyses are based on the patients with T1D.

    Results

    C-peptide was lower in younger children, 0–10 years of age (0.23 ± 0.20 nmol/L) than in older children, 11–18 years of age (0.34 ± 0.28 nmol/L) (p  < 0.000 ). There was a seasonal variation in non-fasting serum C-peptide, significantly correlated to the seasonal variation of diagnosis (p < 0.01). Most children were diagnosed in January, February and March as well as in October when C-peptide was highest, whereas fewer patients were diagnosed in April and May when serum C-peptide was significantly lower (p < 0.01). The seasonal variation of C-peptide was more pronounced in boys than in girls (p < 0.000 and p < 0.01, respectively). Girls had higher C-peptide than boys (p < 0.05), especially in early puberty.

    Conclusions

    Both seasonal and gender differences in residual beta cell function exist already at diagnosis of T1D. These observations have consequences for treatment and for randomizing patients in immune intervention clinical trials.

  • 46.
    Samuelsson, Ulf
    et al.
    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.
    Lindell, Nina
    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.
    Bladh, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Akesson, Karin
    Ryhov County Hospital, Sweden; Futurum Academic Health and Care, Sweden; Jonköping University, Sweden.
    Carlsson, Annelie
    Lund University, Sweden.
    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.
    Caesarean section per se does not increase the risk of offspring developing type 1 diabetes: a Swedish population-based study2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no 11, p. 2517-2524Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Some studies have revealed a relationship between Caesarean section (CS) and type 1 diabetes, while other studies have not. By using the Swedish paediatric quality register we investigated whether birth by CS is related to the risk of developing type 1 diabetes during childhood. Methods All children diagnosed with type 1 diabetes from 2000 to 2012 and included in the register (n= 9,376) were matched with four controls by year, day of birth, sex and county of birth from the Swedish Medical Birth Register. Results Overall, 13.5% of deliveries were by CS. By group, 14.7% of children who developed type 1 diabetes were delivered by CS compared with 13.3% of control children (p less than 0.001). Mothers with diabetes more often gave birth by CS than mothers without diabetes (78.8% vs 12.7%, p less than 0.001). In a logistic regression model adjusting for maternal age, maternal diabetes and BMI in early pregnancy, the OR for CS was 1.0. A child who developed type 1 diabetes and had a mother with type 1 diabetes at the time of delivery had the highest OR to have been born by CS. Children of mothers without diabetes, delivered by CS, had no increased risk of developing type 1 diabetes. Maternal diabetes was the strongest predictor of childhood diabetes (OR 3.4), especially if the mother had type 1 diabetes (OR 7.54). Conclusions/interpretation CS had no influence on the risk of type 1 diabetes during childhood or adolescence. However, maternal diabetes itself strongly increased the risk of offspring developing type 1 diabetes.

  • 47.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Seasonal variation of birth month and breastfeeding in children with diabetes mellitus2001In: Journal of Pediatric Endocrinology & Metabolism (JPEM), ISSN 0334-018X, E-ISSN 2191-0251, Vol. 14, no 1, p. 43-46Article in journal (Refereed)
    Abstract [en]

    Objective: As breastfeeding is suggested to protect against diabetes mellitus we decided to investigate whether the seasonal variation of month of birth of diabetic children, with more diabetes in children born in summer, can be explained to some extent by a seasonal variation of exclusive breastfeeding. Patients: A population-based group of 297 children who had been diagnosed with diabetes mellitus before the age of 15 years was compared with 792 matched healthy subjects. Results: There was no difference in duration of breast-feeding between children who later got diabetes and the controls. Children (both diabetics and controls) born during the summer were exclusively breastfed for a mean period of 2.2 months. Corresponding figures for children born during winter were 2.8 months (p<0.04), spring 2.5 months (n.s.) and autumn 2.7 months (p<0.05). Seasonality was most pronounced in children who developed diabetes between the ages of 10 and 15 years. Conclusion: These results indicate that children born during the summer, who have increased risk of developing diabetes mellitus, have also been exclusively breastfed for a shorter time.

  • 48.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    The concentrations of short-chain fatty acids and other microflora-associated characteristics in faeces from children with newly diagnosed Type 1 diabetes and control children and their family members2004In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 21, no 1, p. 64-67Article in journal (Refereed)
    Abstract [en]

    Aims: The gut flora is quantitatively the most important source of microbial stimulation and may provide a primary signal in the maturation of the immune system. We compared the microflora-associated characteristics (MACs) in 22 children with newly diagnosed diabetes, 27 healthy controls, and their family members to see if there were differences between the children and if there was a familial pattern. Methods: The MACs were assessed by determining the concentrations of eight short-chain fatty acids (SCFA), mucin, urobilin, b-aspartylglycine, coprastanol and faecal tryptic activity (FTA). Results: There were no statistically significant differences between the concentrations of SCFA in the diabetes and control children. Members of families with a diabetic child had a higher concentration of acetic acid (P < 0.02) and lower concentrations of several other SCFAs than control families (P < 0.05-0.02). The other MACs showed no differences between the children or between the two family groups. Conclusion: In this pilot study we saw no differences in the MACs between children with diabetes and their controls. There were, however, some differences between the family members of diabetic children and controls that may indicate a familial pattern regarding the production of SCFAs by the gut flora. The role of the gut flora in relation to the risk of developing Type 1 diabetes needs to be analysed in larger and/or prospective studies.

  • 49.
    Samuelsson, Ulf
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Barn.
    When should determination of ketonemia be recommended?2002In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 4, no 5, p. 645-650Article in journal (Refereed)
    Abstract [en]

    Diabetic ketoacidosis is a serious complication of type diabetes. β-Hydroxybutyrate (β-OHB) accounts for about 75% of ketones, and blood concentration can be determined with a sensor. The aim of this study was to investigate the frequency and degree of ketonemia in daily life of children with diabetes and to make a base for recommendations for determination of ketonemia in clinical practice. During 3 months 45 patients with type 1 diabetes since 1-10 years old (mean 4.4 ± 3.3 years old) at the pediatric clinic in Linköping, Sweden, performed 24-h profiles (eight determinations) in 2 weeks with blood glucose and β-OHB. The children performed 11,189 blood glucose and 7,057 β-OHB measurements. Only 0.3% (n = 21) of β-OHB measurements were ≥ 1.0 mmol/L. An β-OHB concentration > 0.2 mmol/L was more common in the morning than during the rest of the day (p < 0.001). Young children (4-7 years old) had values ≥ 0.2 mmol/L more often than adolescents (p < 0.001). Blood glucose values > 15 mmol/L were more often accompanied by β-OHB > 0.2 mmol/L (p < 0.001). High β-OHB concentrations are rare in diabetic children with reasonably good metabolic control. Already a value > 0.4 mmol/L seems abnormal, and we recommend that patients retest glucose and ketones with β-OHB > 0.4 mmol/L. Furthermore, we recommend that diabetic children and adolescents measure β-OHB when symptoms like nausea or vomiting occur to differentiate ketoacidosis from gastroenteritis, and during infections, during periods with high blood glucose (> 15 mmol/L), and if they notice ketonuria. Monitoring β-OHB should be routine for patients on pump therapy.

  • 50.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Löfman, Owe
    Norwegian University of Life Science, Norway.
    Geochemical Correlates to Type 1 Diabetes Incidence in Southeast Sweden: An Environmental Impact?2014In: Journal of environmental health, ISSN 0022-0892, Vol. 76, no 6, p. 146-154Article in journal (Refereed)
    Abstract [en]

    The authors aim was to explore whether geological factors contribute to geographical variation in the incidence of type 1 diabetes. All children diagnosed with type 1 diabetes in southeastern Sweden during 1977-2006 were defined geographically by their place of residence and were allocated x and y coordinates in the national grid. The population at risk, all children 0-16 years of age, was geocoded in a similar manner. Three of the analyzed minerals in moraine and one of the analyzed minerals in brook water plants were significantly associated with type 1 diabetes at the time of diagnosis. Additionally, the birthplace of the children who subsequently developed diabetes differed in relation to some of the minerals. In communities with high incidence and in communities with low incidence, children were diagnosed with type 1 diabetes in areas with the same high or low level of elements. The authors findings in their pilot study indicate a possible geographical covariation of incidence and some geological factors.

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