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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.
    Birkebaek, N. H.
    et al.
    Aarhus Univ, Denmark.
    Kahlert, J.
    Aarhus Univ Hosp, Denmark.
    Bjarnason, R.
    Landspitali Univ Hosp, Iceland; Univ Iceland, Iceland.
    Drivvoll, A. K.
    Oslo Univ Hosp, Norway.
    Johansen, A.
    Rigshosp, Denmark.
    Konradsdottir, E.
    Landspitali Univ Hosp, Iceland; Univ Iceland, Iceland.
    Pundziute-Lycka, A.
    Queen Silvia Childrens Hosp, 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, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Skrivarhaug, T.
    Oslo Univ Hosp, Norway.
    Svensson, J.
    Univ Copenhagen, Denmark.
    Body mass index standard deviation score and obesity in children with type 1 diabetes in the Nordic countries. HbA(1c) and other predictors of increasing BMISDS2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 7, p. 1198-1205Article in journal (Refereed)
    Abstract [en]

    Background: Intensified insulin therapy may increase body weight and cause obesity. This study compared body mass index standard deviation score (BMISDS) and obesity rate in children with type 1 diabetes (T1D) in Denmark, Iceland, Norway and Sweden, and uncovered predictors for increasing BMISDS. Methods: Data registered in the Nordic national childhood diabetes databases during the period 2008-2012 on children below 15 years with T1D for more than 3 months were compiled, including information on gender, age, diabetes duration, hemoglobin A(1c) (HbA(1c)), insulin dose, severe hypoglycemia (SH), treatment modality, height and weight. The Swedish reference chart for BMI was used for calculating BMISDS. Results: Totally, 11025 children (48% females) (30994 registrations) were included. Medians by the last recorded examination were: age, 13.5 years; diabetes duration, 4.3 years; HbA(1c), 7.9% (63 mmol/mol); insulin dose, 0.8 IU/kg/d and BMISDS, 0.70. Obesity rate was 18.5%. Adjusted mean BMISDS (BMISDS adj) was inversely related to HbA(1c) and directly to diabetes duration. Higher BMISDS adj was found in those with an insulin dose above 0.6 IU/kg/d, and in girls above 10 years. Pump users had higher BMISDS adj than pen users, and patients with registered SH had higher BMISDS adj than patients without SH (both P amp;lt; .001). Conclusion: Obesity rate in children with T1D in the Nordic countries is high, however, with country differences. Low HbA(1c), long diabetes duration, higher insulin dose, pump treatment and experiencing a SH predicted higher BMISDS. Diabetes caregivers should balance the risk of obesity and the benefit of a very low HbA(1c).

  • 5. Brekke, Hilde
    et al.
    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.
    Vitamin D supplementation and diabetes-related autoimmunity in the ABIS study2007In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 8, no 1, p. 11-14Article in journal (Refereed)
    Abstract [en]

    Supplementation with vitamin D during infancy, as well as intake of vitamin D during pregnancy, has been associated with decreased risk of type 1 diabetes or diabetes-related autoantibodies in children. The primary aim of this report was to investigate whether vitamin D supplementation during infancy is associated with diabetes-related autoimmunity at 1 and 2.5 yr in the children. Second, we examined whether consumption of vitamin-D-containing supplements during pregnancy is related to risk of autoimmunity in the offspring. Screening questionnaires were completed for 16 070 infants after delivery, including a food-frequency questionnaire regarding the mother's use of dietary supplements during pregnancy. Parents of 11 081 and 8805 infants completed a follow-up questionnaire regarding the use of vitamin supplementation at 1 and 2.5 yr, respectively. Autoantibodies against glutamic acid decarboxylase and islet antigen-2 (IA-2) were analyzed in whole blood from 8694 children at 1 yr and 7766 children at 2.5 yr. Supplementation with AD-drops was not associated with autoantibodies at 1 or 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced diabetes-related autoimmunity at 1 yr (adjusted odds ratio: 0.707, confidence interval: 0.520-0.962, p = 0.028) but not at 2.5 yr. In conclusion, no association was found between an intermediate dose of vitamin D supplementation during infancy and development of diabetes-related autoantibodies at 1 and 2.5 yr. Use of vitamin-D-containing supplements during pregnancy was associated with reduced development.

  • 6.
    Carlsson, Annelie
    et al.
    Lund University, Sweden .
    Forsander, Gun
    Sahlgrens University Hospital, 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.
    Larsen, Sara
    Novo Nordisk Scandinavia AB, Sweden .
    Ortqvist, Eva
    Karolinska University Hospital, Sweden .
    A multicenter observational safety study in Swedish children and adolescents using insulin detemir for the treatment of type 1 diabetes2013In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, no 5, p. 358-365Article in journal (Refereed)
    Abstract [en]

    This 26-wk observational study in children and adolescents with type 1 diabetes (T1D) in Sweden investigated the safety and efficacy of insulin detemir (IDet) in newly diagnosed (ND) patients and those with established diabetes (ED) switching to IDet. A total of 159 patients initiated IDet as part of basal-bolus therapy, 59 in the ND stratum (mean age 9.7yr) and 97 in the ED stratum (mean age 12.5 yr). The primary outcome measure was the incidence of severe adverse drug reactions; just one major hypoglycemic event occurred in a patient in the ND stratum during the study and one patient was withdrawn due to injection-site reactions. All other events were classified as mild. In the ED stratum, there was a reduction in hypoglycemic events in the 4wk prior to study end from baseline (mean reduction of 2.46 events, not significant) and a significant reduction in nocturnal hypoglycemia (mean reduction of 2.24 events, p=0.0078). Glycemic control improved in the ND stratum as expected and, in the ED stratum, there was no significant change in HbA1c from baseline (mean reduction of -0.45%). At study end, mean daily IDet doses were 0.39U/kg (ND) and 0.54U/kg (ED). Weight increased by 5.7 and 2.0kg in the ND and ED strata, respectively, and was within the normal limits for growing children. IDet provided good glycemic control and was well tolerated, with a reduced risk of nocturnal hypoglycemia in a heterogeneous cohort of children and adolescents with T1D.

  • 7.
    Couper, Jennifer J.
    et al.
    Womens and Childrens Hospital, Australia; University of Adelaide, Australia; University of Adelaide, Australia.
    Haller, Michael J.
    University of Florida, FL USA.
    Ziegler, Annette-G
    Technical University of Munich, Germany; Technical University of Munich, Germany.
    Knip, Mikael
    University of Helsinki, Finland.
    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.
    Craig, Maria E.
    Childrens Hospital Westmead, Australia; University of Sydney, Australia; University of New S Wales, Australia .
    Phases of type 1 diabetes in children and adolescents2014In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 15, p. 18-25Article in journal (Refereed)
    Abstract [en]

    n/a

  • 8.
    Danne, Thomas
    et al.
    Hannover, Tyskland .
    Battelino, Tadej
    Ljubljana, Slovenien .
    Kordonouri, Olga
    Berlin, Tyskland .
    Hanås, Ragnar
    Barnklin, Uddevalla .
    Klinkert, Christof
    Bad Oeynhausen, Tyskland .
    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.
    Barrio, Raquel
    Madrid, Spanien.
    Aebi, Christine
    Wildermeth, Schweiz .
    Gschwend, Sylvia
    Biel, Schweiz .
    Mullis, Primus-E
    Zug, Schweiz .
    Schumacher, Urs
    Munsterlingen, Schweiz .
    Zumsteg, Urs
    Basel, Schweiz .
    Morandi, Anita
    Verona, Italy .
    Rabbone, Ivana
    Turin, Italien .
    Cherubini, Valentino
    Marche, Italien .
    Toni, Sonia
    Florence, Italien .
    de Beauforte, Carine
    Luxemburg .
    Hindmarsh, Peter
    London, UK .
    Sumner, Alex
    Peterborough, UK.
    van Waarde, Willie M
    Groningen, Holland .
    van den Berg, Norbert
    Almere, Holland .
    Phillip, Moshe
    Petah Tikva Israel.
    A cross-sectional international survey of continuous subcutaneous insulin infusion in 377 children and adolescents with type 1 diabetes mellitus from 10 countries2005In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 6, no 4, p. 193-198Article in journal (Refereed)
    Abstract [en]

    Objective: To document current practices using continuous subcutaneous insulin infusion (CSII) by downloading electronically the 90-d pump data held within the pump memory and relating that to clinical data from children and adolescents in different pediatric diabetes centers from Europe and Israel. Methods: Data of patients (1-18 yr) treated with CSII in 23 centers from nine European countries and Israel were recorded with the ENCAPTURE software (PEC International, Frankfurt, Germany). The number of patients who participated was 377 (48% female, mean diabetes duration ± SD: 6.8 ± 3.7 yr, age: 12.9 ± 3.8 yr, preschool n = 33, prepubertal n = 95, adolescent n = 249, CSII duration: 1.6 ± 1.2 yr, local HbA1c: 8.1 ± 1.2%). Results: The total insulin dose was lower than previously reported for injection therapy (0.79 ± 0.20 U/kg/d). Covariance coefficient of daily total insulin was high in all age groups (adolescents 19 ± 9%, prepubertal 18 ± 8 and preschool 17 ± 8). The distribution of basal insulin infusion rates over 24 hr (48 ± 12% of total dose) varied significantly between centers and age groups. The number of boluses per day (7 ± 3) was not significantly different between the age groups (average daily bolus amount: 0.42 ± 0.16 U /kg). The rate of severe hypoglycemia (coma/convulsions) was 12.4 episodes per 100 patient-years and the number of diabetes-related hospital days was 124 per 100 patient-years. Discussion: Pediatric CSII patients show a high variability in their insulin therapy. This relates both to age-dependent differences in the distribution of basal insulin as to the age-independent day-to-day variation in prandial insulin. © Blackwell Munksgaard, 2005.

  • 9.
    Delli, Ahmed J.
    et al.
    Lund University.
    Lindblad, Bengt
    Queen Silvia Childrens Hospital.
    Carlsson, Annelie
    University Lund Hospital.
    Forsander, Gun
    Queen Silvia Childrens Hospital.
    Ivarsson, Sten-A
    Lund University.
    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, Claude
    Karolinska University Hospital.
    Lernmark, Ake
    Lund University.
    Type 1 diabetes patients born to immigrants to Sweden increase their native diabetes risk and differ from Swedish patients in HLA types and islet autoantibodies2010In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 11, no 8, p. 513-520Article in journal (Refereed)
    Abstract [en]

    Aim: To determine whether type 1 diabetes mellitus (T1DM) patients, having parents who immigrated to Sweden, have increased T1DM risk before 18 yr compared with countries of origin. We also determined whether they have different human leukocyte antigen (HLA) genetic markers and islet autoantibodies at diagnosis compared with Swedish patients. Methods: A total of 1988 (53% males) newly diagnosed and confirmed T1DM patients less than 18 yr registered within the Better Diabetes Diagnosis (BDD) study (May 2005 to September 2008) were included. Participants were classified into three groups: Swedish, non-Swedish, and Mixed-origin patients according to country of origin of two generations (parents and grandparents). These groups were compared with respect to T1DM HLA markers and islet autoantibodies [glutamic acid decarboxylase autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and islet antigen-2 autoantibodies (IA-2Ab)]. Results: Only 30 (1.5%) patients were born outside Sweden. Swedish patients constituted 66%, non-Swedish patients 8%, Mixed origins 17%, and 9% were of uncertain origin. Confirmed T1DM in patients within the study was 22 (95% CI: 21-23) patients/105/yr rate for Swedish patients compared with 14 (95% CI: 13-15) among non-Swedish patients. The HLA-DQ8 haplotype (p less than 0.0001) and DQ2/8 genotype (p less than 0.02) predominated among Swedish compared with non-Swedish patients. In contrast, DQ2 was the most frequent haplotype among non-Swedish patients [OR = 1.5 (95% CI: 1.0-2.0), p less than 0.04]. Multiple (greater than= 2) autoantibodies (p less than 0.04) and specifically IA-2Ab (p less than 0.001) were most prevalent among the Swedish patients. Multiple autoantibodies were associated with DQ8 among the Swedish patients only (p less than 0.001). Conclusion: Patients born to parents who had immigrated to the high T1DM incidence environment of Sweden have, compared with Swedish patients, more frequent HLA-DQ2 genetic markers and are diagnosed more often with GAD65Ab.

  • 10.
    Enander, Rebecka
    et al.
    SkaS Hosp Grp, Sweden.
    Adolfsson, Peter
    Hosp Halland, Sweden; Univ Gothenburg, Sweden.
    Bergdahl, Torun
    SkaS Hosp Grp, Sweden.
    Forsander, Gun
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Hanas, Ragnar
    Univ Gothenburg, Sweden; NU Hosp Grp, Sweden.
    Beta cell function after intensive subcutaneous insulin therapy or intravenous insulin infusion at onset of type 1 diabetes in children without ketoacidosis2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 6, p. 1079-1085Article in journal (Refereed)
    Abstract [en]

    Background

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

    Methods

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

    Results

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

    Conclusion

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

  • 11.
    Forsander, Gun
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Bogelund, Mette
    Incentive, Denmark.
    Haas, Josephine
    Karolinska Institute, Sweden.
    Samuelsson, Ulf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Adolescent life with diabetes-Gender matters for level of distress. Experiences from the national TODS study2017In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 18, no 7, p. 651-659Article in journal (Refereed)
    Abstract [en]

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

  • 12.
    Granfors, Maria
    et al.
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Augustin, Hanna
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Göteborg.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Brekke, Hilda K
    Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg.
    No association between use of multivitamin supplement containing vitamin D during pregnancy and risk of Type 1 Diabetes in the child2016In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 17, no 7, p. 525-530Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

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

    METHODS:

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

    RESULTS:

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

    CONCLUSION:

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

  • 13.
    Gullstrand, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Wahlberg Topp, Jeanette
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Ilonen, Jorma
    Dept of Microbiology Kuopio, Finland.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    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.
    Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study2008In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, no 3 PART 1, p. 182-190Article in journal (Refereed)
    Abstract [en]

    Background: Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children. Methods: T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study. Results: GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies. Conclusions: The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response. © 2008 The Authors Journal compilation © 2008 Blackwell Munksgaard.

  • 14.
    Hanberger, Lena
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    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, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Holl, Reinhard W.
    Univ Ulm, Germany; German Inst Diabet Res, Germany.
    Froehlich-Reiterer, Elke
    Med Univ Graz, Austria.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden; Jonkoping Univ, Sweden.
    Hofer, Sabine
    Med Univ Innsbruck, Austria.
    Type 1 diabetes during adolescence: International comparison between Germany, Austria, and Sweden2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 3, p. 506-511Article in journal (Refereed)
    Abstract [en]

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

  • 15.
    Hanås, Ragnar
    et al.
    Department of Pediatrics, Uddevalla Hospital.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Hypoglycemia and ketoacidosis with insulin pump therapy in children and adolescents2006In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 7, no Supp. 4, p. 32-38Article in journal (Refereed)
    Abstract [en]

    This review deals with the two most serious side effects encountered with insulin pump therapy, severe hypoglycemia and diabetic ketoacidosis (DKA). Although clinical follow-up studies reported decreased rates of severe hypoglycemia, randomized studies have not confirmed this, showing no difference between the pump and injection groups. Less-severe hypoglycemia (mild/moderate/symptomatic hypoglycemia) was found to be more common with pump use. Some patients have inadvertently dosed or overdosed while awake or during sleep, causing fatal outcome in rare cases. Population-based or retrospective clinical studies reported a low rate of DKA in pump users that was still a higher rate than those using injection therapy, at least in some countries. In research settings and for patients with good compliance and adequate family support, the risk of DKA seems lower; many short-term studies report no DKA at all, possibly due to the increased attention given to participants. The use of continuous subcutaneous insulin infusion (CSII) seems to decrease the risk in patients who had recurrent DKA before pump start. Most episodes of DKA occur early after pump start, suggesting a learning curve occurs in all new forms of treatment. Increased teaching and awareness programs are vital to prevent severe hypoglycemia and DKA in children and adolescents using insulin pumps.

  • 16.
    Hanås, Ragnar
    et al.
    Department of Pediatrics, Uddevalla Hospital, Sweden.
    Lytzen, Lene
    Novo-Nordisk A/S, 2880 Bagsvaerd, Denmark.
    Ludvigsson, Johnny
    Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Thinner needles do not influence injection pain, insulin leakage or bleeding in children and adolescents with type 1 diabetes2000In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 1, no 3, p. 142-149Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate pain, leakage and bleeding when injecting insulin with different diameters of needles.

    Methods: Sixty children and adolescents aged 9–21 yrs participated in study A and 40 aged 8–20 yrs in study B. Both were double-blind and randomized. In study A, we evaluated the pain when injecting with three needles [Novo 27G/13 mm (N27), B-D MicroFine IV 28G/13 mm (B28), NovoFine 28G/12 mm (N28)] and in study B, with three needles [NovoFine 28G/12 mm (N28), B-D MicroFine+ 29G/13 mm (B29), NovoFine 30G/8 mm (N30)] and one placebo injection (no needle mounted). Abdominal and thigh injections were given in a 45° angle with a lifted two-finger skinfold on two different visits, scoring pain on a 10-cm visual analog scale (VAS), and in study B faces were added to the scale.

    Results: The median VAS scores in study A were 1.2 cm (N27), 1.2 cm (B28) and 1.0 cm (N28) for abdominal injections, and 1.2 cm (N27), 0.7 cm (B28) and 1.1 cm (N28) (n.s.) for thigh injections. The median VAS scores in study B were 2.5 cm (N28), 2.3 cm (B29) and 2.8 cm (N30) (n.s.) for abdominal injections, and 2.0 cm (N28), 1.5 cm (B29) and 1.9 cm (N30) (n.s.) for thigh injections. The overall median score of placebo injections was 0.1 cm (p=0.0001). Bleedings were less common with the B29 needle (35.5%) than with the N28 needle (48.1%) (p=0.028) but with no difference compared to the N30 needle (39.2%). Leakage of insulin was found in 14% of abdominal and 25% of thigh injections (p=0.0001) with no difference between the needles. VAS scores were higher in study B which may be explained by the facial VAS scale increasing the range of answers.

    Conclusions: We found no difference in injection pain, preference, bleeding or insulin leakage between the needles. Decreasing the needle diameter from 0.4 to 0.3 mm (27–30G) does not seem to decrease pain perception in this age group.

  • 17.
    Helgesson, G.
    et al.
    Karolinska Institutet.
    Hansson, M.G.
    Uppsala University.
    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.
    Swartling, Ulrica
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Practical matters, rather than lack of trust, motivate non-participation in a long-term cohort trial2009In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 10, no 6, p. 408-412Article in journal (Refereed)
    Abstract [en]

    Objective: The objective of this study was to investigate the importance of trust in researchers and other reasons that participating parents, former participants, and non-participants had for participating, or not participating, in a longitudinal cohort study on prediction and development of diabetes in children. Study design: A questionnaire addressing each of these groups, where respondents graded the importance of a set of listed reasons for participating/not participating, was randomly distributed to 2500 families in the All Babies in Southeast Sweden (ABIS) study region with children born between 1997 and 1999. Results: Lack of trust was not a central factor to a great majority of respondents who decided not to participate in the ABIS study or who later decided to opt out. Practical matters, like blood sampling and lack of time, were important factors to many more. Yet, four fifths of those who still participate in the ABIS study stated trust in the researchers to be an important factor to their initial decision to participate. Conclusions: Trust in researchers may be a necessary prerequisite in order for people to be willing to participate in research, but practical matters such as time that has to be spent or pain involved in collecting blood were more important factors than lack of trust in explaining opt out in relation to the ABIS study.

  • 18.
    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.

  • 19.
    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.
    Immune intervention at diagnosis - Should we treat children to preserve beta-cell function?2007In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 8, no SUPPL. 6, p. 34-39Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes (T1D) is characterized by loss of beta-cell function. If beta-cell function can be preserved, it will lead to improved metabolic balance with improved quality of life and fewer acute and late complications, and if residual insulin secretion improves well enough, then that could lead to complete remission and even cure of the disease. Several efforts to save residual beta-cell function have been made for more than three decades without success. Proof of principle has been possible, and it seems clear that immune suppression or immune modulation, in fact, can stop the destructive process and thereby preserve beta-cell function. However, the effect seen in adult patients with T1D have been minimal or absent in diabetic children who seem to have another or at least more aggressive disease process. Furthermore, the immune interventions have had too serious and common adverse events in comparison to the scarce-positive effect. Recent more specific immune modulation with anti-CD3 monoclonal antibodies seems more encouraging with at least postponement of the C-peptide decline, but unfortunately still with common and quite threatening adverse effects. Even more promising are the autoantigen therapies, of which glutamic acid decarboxylase (GAD) vaccination has shown good results with impressive preservation of residual insulin secretion in 10- to 18-year-old type 1 diabetic patients with recent onset. In patients with short diabetes duration at intervention the effect was remarkable. Furthermore, these effects were achieved with no adverse events. Future studies will show whether the good effect seen so far can be confirmed. If so there is hope that GAD vaccination will cause remission and even cure and prevention of T1D will then no longer be just a dream. © 2007 The Authors Journal compilation.

  • 20.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus Linköping/Motala.
    No acute pancreatitis but reduced exocrine pancreatic function at diagnosis of type 1 diabetes in children2019In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448Article in journal (Refereed)
    Abstract [en]

    Background Insulitis in type 1 diabetes (T1D) seems to be both mild and rather rare, and immune cells are found also in the exocrine pancreas, which often is small. We wanted to see whether clinical pancreatitis at diagnosis of T1D in children is a commonly missed diagnosis. Methods Clinical symptoms suggesting pancreatitis were investigated in a retrospective case-control study in 191 newly diagnosed T1D patients (105 boys, 86 girls) with age at onset 0.2 to 18 (mean = 10.05, SD = 4.71, median = 10.36) years, 23/191 (12%) with ketoacidosis at diagnosis. Blood samples were taken on day 4 and stored at -20 degrees C until analyses for P-amylase and C-reactive protein (CRP), and compared with 100 age-matched healthy control children with plasma stored at -80 degrees C, and 46 with plasma stored at -20 degrees C. Results At diagnosis, 23/191 (12%) patients had mild transient abdominal pain, 2/23 with obstipation, and 5/23 also transient mild diarrhea. Five of 23 patients with abdominal pain had pH amp;lt; 7.30. None had clinical acute pancreatitis. One diabetic patient had P-amylase 1.3 mu kat/L (normal range = 0.15-1.1 mu kat/L), while 62/191 (32.4%) diabetic children had P-amylase below the normal range. None (0/100) of the -80-controls and only 1/46 (0.14 mu kat/L) of the -20-controls had the P-amylase level in the normal range. Five diabetic children, but no controls, had increased CRP, but not related to P-amylase or to gastrointestinal symptoms. Conclusions Acute pancreatitis seems to be very rare at diagnosis of T1D, but decreased exocrine function quite common, which supports that T1D sometimes is part of a more generalized pancreatic disorder.

  • 21.
    Ludvigsson, Johnny
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Primary prevention of type 1A diabetes: are we there yet?2007In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 8, no 3, p. 115-116Article in journal (Other academic)
  • 22.
    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.

  • 23.
    Ludvigsson, Johnny
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Lefebvre, Pierre
    Univ Liege, Belgium.
    Nerup, Jorn
    Gentofte Univ Copenhagen, Denmark.
    It is time to restore Rules for Authorship of scientific publications2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 3, p. 586-586Article in journal (Other academic)
    Abstract [en]

    n/a

  • 24.
    Nilsson, John
    et al.
    Ryhov County Hospital, Sweden.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Sweden; Jonköping University, Sweden; Jonköping University, 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 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.
    High HbA1c at onset cannot be used as a predictor for future metabolic control for the individual child with type 1 diabetes mellitus2017In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 18, no 8, p. 848-852Article in journal (Refereed)
    Abstract [en]

    BackgroundTo study how metabolic control at onset of type 1 diabetes correlates to metabolic control and clinical parameters during childhood until transition from pediatric care to adult diabetes care. Materials and MethodsData at onset, three months, one, three, and five years after diagnosis and at transition, on HbA1c and clinical parameters, on 8084 patients in the Swedish pediatric quality registry, SWEDIABKIDS, were used. Of these patients, 26% had been referred to adult diabetes care by 2014. ResultsChildren with HbA1c amp;lt; 72mmol/mol (8.7%) (20% of patients, low group) at diagnosis continued to have good metabolic control during childhood, in contrast to children with HbA1c amp;gt; 114mmol/mol (12.6%) (20% of patients, high group) at diagnosis, who continued to have high HbA1c at follow-up. For the individual, there was no significant correlation between high HbA1c at onset and during follow-up. During follow-up, children in the high group were more often smokers, less physically active, and more often had retinopathy than children in the low group (Pamp;lt;.01, .01, .03 respectively). ConclusionHigh HbA1c at onset was associated with high HbA1c during follow-up on a group level, but it cannot be used as a predictor of future metabolic control on an individual level. These results emphasize the important work done by the diabetes team in the first years after diagnosis. It is important to continuously set high goals for the achievement of tight metabolic control, in order to decrease the risk of microvascular complications.

  • 25.
    Oberg, Daniel
    et al.
    Vastervik Hosp, Sweden.
    Salemyr, Jenny
    Karolinska Inst, Sweden; Univ Hosp, Sweden.
    Ortqvist, Eva
    Karolinska Inst, Sweden; Univ Hosp, Sweden.
    Juul, Anders
    Rigshosp, Denmark; Univ Copenhagen, Denmark.
    Bang, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    A longitudinal study of serum insulin-like growth factor-I levels over 6 years in a large cohort of children and adolescents with type 1 diabetes mellitus: A marker reflecting diabetic retinopathy2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 5, p. 972-978Article in journal (Refereed)
    Abstract [en]

    Objective

    To evaluate longitudinal serum insulin‐like growth factor‐I (IGF‐I) in a large cohort of children and adolescents with type 1 diabetes in relation to hemoglobin A1c (HbA1c), age, diabetes duration, and body mass index (BMI), its association to height and retinopathy, and in comparison with healthy subject references.

    Methods

    A total of 2683 serum IGF‐I values were obtained from 806 children and adolescents with T1DM, from annual blood samples for up to 6 consecutive years.

    Results

    In a multiple regression analysis IGF‐I values were negatively correlated to HbA1c and diabetes duration, and positively correlated to BMI (P < .001, P < .001, and P < .001, respectively, adjusted r2 = 0.102). Children and adolescents with T1DM had lower mean IGF‐I levels and reference interval limits compared to healthy subjects. In boys, mean (SD) IGF‐I SD score (SDS) levels were −1.04 (±1.3) calculated from the healthy reference. IGF‐I peaked at 15 years of age, similarly to healthy controls, but with markedly lower levels in late puberty. Girls were more affected at later stages of puberty but with a slightly less depressed overall mean IGF‐I SDS of −0.69 (±1.2). In a subgroup of 746 subjects with fundus photography, a negative correlation was seen between individual mean IGF‐I SDS and preproliferative retinopathy (P = .004, adjusted r2 = 0.021). In another subgroup of 84 adolescents, no correlation was seen between individual mean IGF‐I SDS and target height SDS or distance to target height SDS.

    Conclusion

    Poor metabolic control and diabetes duration impact negatively on serum IGF‐I levels. A low individual mean IGF‐I level was associated with progression of retinopathy independently of HbA1c, age, gender, and diabetes duration. Disease, sex and age related IGF‐I SDS may become clinical helpful as a supplement to HbA1c in predicting the long‐term outcome for children and adolescents with T1DM.

  • 26.
    Olsen Faresjö, Åshild
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Pet exposure in the family during pregnancy and risk for type 1 diabetes: The prospective ABIS study2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 7, p. 1206-1210Article in journal (Refereed)
    Abstract [en]

    Background: The autoimmune process later leading to type 1 diabetes (T1D) seems to start very early in life. Different viruses have been suspected to contribute to the development of T1D, some already during pregnancy. As viruses may be hosted by animals and from them transferred to humans we decided to investigate if exposure to pets during pregnancy is related to later development of T1D. Methods: ABIS (All Babies in Southeast Sweden)-is a prospective population-based cohort study of unselected children born in southeast Sweden between Oct first 1997 to Oct first 1999. Parents of 16384 children answered a questionnaire within 3 days after birth including information about exposure to different pets. The ABIS registry has been connected to the National Registry of diagnosis and also the national Registry of Drug prescriptions so we know that 137 children have got T1D, and they were compared with the non-diabetic population. Results: During pregnancy, 45.5% of the mothers had pet animals at home. Most common were cats (25.0%) and dogs (18.7%). Neither exposure to dogs (OR = 1.27, P = 0.23) or cats (OR = 0.81, P = 0.31) were associated to later T1D risks. However, exposure to hamsters increased the T1D risk (OR 4.21, P = 0.0007). In a multiple regression this association remained (P = 0.005) when adjusted for other possible risk factors. Conclusions: Exposure to hamster during pregnancy seems to increase the risk of T1D in the child. One possibility could be infection by virus hosted by the pet.

  • 27.
    Petersson, Jonathan
    et al.
    Orebro Univ, Sweden.
    Åkesson, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Sundberg, Frida
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden.
    Sarnblad, Stefan
    Orebro Univ, Sweden; Univ Hosp Orebro, Sweden.
    Translating glycated hemoglobin A1c into time spent in glucose target range: A multicenter study2019In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, no 3, p. 339-344Article in journal (Refereed)
    Abstract [en]

    Background Approximately 90% of children and adolescents with type 1 diabetes in Sweden use continuous glucose monitoring (CGM), either as real-time CGM or intermittently scanned CGM to monitor their glucose levels. Time in target range (TIT) is an easily understandable metric for assessing glycemic control. Objective The aim of this study was to examine the relation between TIT and hemoglobin A1c (HbA1c). Subjects and Methods Subjects were recruited from three diabetes care centers in Sweden. Glucose data were collected for 133 children and adolescents with type 1 diabetes through CGM using Diasend. Subjects with registration time over 80% were included in the analysis. HbA1c was collected from SWEDIABKIDS, the Swedish pediatric diabetes quality registry. TIT was defined as 3.9 to 7.8 mmol/L (70-140 mg/dL) and time in range (TIR) as 3.9 to 10 mmol/L (70-180 mg/dL). Results During the period of 60 days, 105 subjects provided complete data for analysis. Mean age was 12.2 (+/- 3.3) years, mean HbA1c was 53.9 (+/- 8.2) mmol/mol or 7.1% (+/- 0.7%). Mean sensor glucose value was 8.6 (+/- 1.3) mmol/L, mean coefficient of variation was 42.2% (+/- 7.2%), mean TIT was 40.9% (+/- SD 12.2%), and mean TIR was 60.8% (+/- 13.1%). There was a significant nonlinear relation between TIT during 60 days and HbA1c, R-2 = 0.69. Conclusion This study suggests a nonlinear relation between time spent in glucose target range and HbA1c. The finding implies that time spent in TIT could be a useful metric in addition to HbA1c to assess glycemic control.

  • 28.
    Salemyr, Jenny
    et al.
    Karolinska Institute and University Hospital, Stockholm.
    Bang, Peter
    Karolinska Institute and University Hospital, Stockholm.
    Örtqvist, Eva
    Karolinska Institute and University Hospital, Stockholm.
    Lower HbA1c after 1 year, in children with type 1 diabetes treated with insulin glargine vs. NPH insulin from diagnosis: a retrospective study2011In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 12, no 5, p. 501-505Article in journal (Refereed)
    Abstract [en]

    Objective: Insulin glargine offers sustained insulin delivery for 24 h. Change to glargine treatment consistently results in lower fasting glucose and fewer hypoglycemic episodes in children with type 1 diabetes compared to continuation of NPH, although glargine has not been shown to improve HbA1c in randomized trials. Studies comparing glargine and NPH in multiple injection therapy in children treated from diagnosis of type 1 diabetes are lacking. Methods: HbA1c and insulin requirement were compared in a retrospective study of children (7-17 yr of age) with type 1 diabetes treated from diagnosis with basal insulin glargine (n = 49) or NPH (n = 49) in a multiple injection therapy (MIT) regimen with a rapid-acting insulin analogue. Patients were followed every third month for 1 yr. HbA1c, insulin dose, and weight data were retrieved. Results: HbA1c (mean +/- SD) was lower at 3-5 months (5.5 +/- 0.89 vs. 6.2 +/- 0.89%, p < 0.05) and 6-9 months (5.6 +/- 1.14 vs. 6.6 +/- 0.99%; p < 0.001) in glargine treated. After 12 months, HbA1c was significantly lower in glargine treated (6.3 +/- 1.56 vs. 7.1 +/- 1.28; p < 0.01). Reported total insulin doses were similar at nadir (0.5 U/kg BW x 24 h), but significantly lower at 12 months in glargine treated (0.64 +/- 0.23 vs. 0.86 +/- 0.3U/kg BW x 24 h; p < 0.001). Conclusions: HbA1c 1 yr from diagnosis was lower in children treated with glargine from start as compared with those on NPH. This observation should be viewed in the light of a significantly lower dose of total daily insulin in the glargine group.

  • 29.
    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.
    Steineck, Isabelle
    Herning Hospital, Denmark .
    Gubbjornsdottir, Soffia
    University of Gothenburg, Sweden .
    A high mean-HbA1c value 3-15 months after diagnosis of type 1 diabetes in childhood is related to metabolic control, macroalbuminuria, and retinopathy in early adulthood - a pilot study using two nation-wide population based quality registries2014In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 15, no 3, p. 229-235Article in journal (Refereed)
    Abstract [en]

    BackgroundIntensive treatment of patients with type 1 diabetes delays the onset of long-term complications. ObjectivesOn the basis of the information from two nation-wide quality registers, we investigated to which extent HbA1c values 3-15months after diagnosis in childhood are related to metabolic control, albuminuria, and retinopathy in early adulthood. MethodsIn Sweden, physicians register all children and adolescents with type 1 diabetes mellitus in the Swedish Pediatric Quality Registry. After 18yr of age, people with diabetes are followed by the Swedish National Diabetes Register. We identified 1543 children and adolescents with a mean age of 13.9yr at diagnosis and a mean duration of type 1 diabetes mellitus of 7.1yr. ResultsChildren and adolescents with poor metabolic control (mean HbA1c 70mmol/mol (8.6 %)) adjacent to diagnosis had a significantly higher mean HbA1c value years later as adults than did patients with a good metabolic control [less than50mmol/mol (6.7%) (pless than0.001)]. The patients in the high group were also less physically active and smoked more as adults. The proportion of females was higher in the poor metabolic group. Patients with a high mean HbA1c 3-15months after diagnosis had significantly more often macroalbuminuria and retinopathy in early adulthood. ConclusionsMetabolic control adjacent to the diagnosis of type 1 diabetes in childhood or adolescence can predict metabolic control in early adulthood. It is therefore very important that pediatric diabetes teams identify key factors for successful early metabolic control. Actively using quality registries may be one such factor.

  • 30.
    Samuelsson, Ulf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Åkesson, Karin
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Peterson, Anette
    Jonkoping Univ, Sweden; Jonkoping Univ, Sweden.
    Hanas, Ragnar
    Uddevalla Cent Hosp, Sweden; Univ Gothenburg, Sweden.
    Hanberger, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Continued improvement of metabolic control in Swedish pediatric diabetes care2018In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, no 1, p. 150-157Article in journal (Refereed)
    Abstract [en]

    Background: To prospectively investigate if the grand mean HbA1c and the differences in mean HbA1c between centers in Sweden could be reduced, thereby improving care delivered by pediatric diabetes teams. Methods: We used an 18-month quality improvement collaborative (QIC) together with the Swedish pediatric diabetes quality registry (SWEDIABKIDS). The first program (IQ-1), started in April 2011 and the second (IQ-2) in April 2012; together they encompassed 70% of Swedish children and adolescents with diabetes. Results: The proportion of patients in IQ-1 with a mean HbA1c amp;lt;7.4% (57 mmol/mol) increased from 26.4% before start to 35.9% at 36 months (P amp;lt; .001), and from 30.2% to 37.2% (P amp;lt; .001) for IQ-2. Mean HbA1c decreased in both participating and non-participating (NP) centers in Sweden, thereby indicating an improvement by a spatial spill over effect in NP centers. The grand mean HbA1c decreased by 0.45% (4.9 mmol/mol) during 36 months; at the end of 2014 it was 7.43% (57.7 mmol/mol) (P amp;lt; .001). A linear regression model with the difference in HbA1c before start and second follow-up as dependent variable showed that QIC participation significantly decreased mean HbA1c both for IQ-1 and IQ-2. The proportion of patients with high HbA1c values (amp;gt;8.7%, 72 mmol/mol) decreased significantly in both QICs, while it increased in the NP group. Conclusions: The grand mean HbA1c has decreased significantly in Sweden from 2010 to 2014, and QICs have contributed significantly to this decrease. There seems to be a spatial spill-over effect in NP centers.

  • 31.
    Skoglund, Camilla
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Chéramy, Mikael
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Casas, Rosaura
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. 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.
    Hampe, Christiane S
    Department of Medicine, University of Washington, Seattle, WA, USA.
    GAD autoantibody epitope pattern after GAD-alum treatment in children and adolescents with type 1 diabetes2012In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 13, no 3, p. 244-250Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis. Previously we have shown that two injections of glutamic acid decarboxylase formulated in alum (GAD-alum) preserved residual insulin secretion in children and adolescents with recent onset type 1 diabetes (T1D), and was accompanied by an increase in GAD autoantibody (GADA) titers. The aim of the present study was to investigate whether GAD-alum treatment affected the GADA epitope pattern.

    Methods. Serum samples of patients treated with GAD-alum (n=33) or placebo (n=27), at baseline and 1, 3, 9, and 15 months after initiation of treatment, were tested for their binding capacity to specific GADA epitopes in an epitope specific radioligand-binding assay with six GAD65-specific recombinant Fab (rFab) (b96.11, DPA, DPD, MICA3, b78 and N-GAD65 mAb).

    Results. For the period included in this study (baseline to 15 months) no difference in variability of binding to any of the tested rFab were observed. However, a higher median response to the b96.11-defined epitope in the first 3 months after the initial injection was observed in GAD-alum treated patients (-8.1%, min -72.4%, max 39.6%) compared to patients receiving placebo (1.5%, min -28.3%, max 28.6%) (p=0.02). This effect was especially evident in GAD-alum treated patients who experienced an increase of more than 100% in their GADA titer from baseline to 3 months (n=27), where we observed an 10.8% (-10.8%, min -72.4%, max 30.5%) increase in binding to the b96.11 epitope over the  first 3 months post initial injection (p=0.04). Subsequently the recognition of the b96.11-defined epitope in the GAD-alum group decreased between 3 and 15 months (8.3%, min -17.1%, max 36.7%) compared to the placebo group (-2.4%, min -32.8%, max 30.1%) (p<0.05) and returned to levels similar to that observed at baseline. Correlations between GADA titer and epitope binding for b96.11 and DPD were observed in the placebo group, but not in the GADalum group, at 3 and 15 months after initial treatment.

    Conclusions/interpretation. We conclude that administration of GAD-alum temporarily induced increased binding to one epitope specificity of GADA.

  • 32. Study Group, TRIGR
    et al.
    Ludvigsson, Johnny
    Study design of the trial to reduce IDDM in the genetically at risk (TRIGR)2007In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 8, no 3, p. 117-137Article in journal (Refereed)
    Abstract [en]

    The hypothesis for this study is that weaning to an extensively hydrolyzed infant formula will decrease the incidence of type 1 diabetes (T1D), as it does in all relevant animal models for the disease. This will be tested in children who carry risk-associated human leukocyte antigen genotypes and have a first-degree relative with T1D. The trial will use a double-blind, prospective, placebo-controlled intervention protocol, comparing casein hydrolysate with a conventional cow's milk (CM)-based formula. A secondary aim is to determine relationships between CM antibodies, a measure of CM exposure, and diabetes-associated autoantibodies. To achieve an 80% power for the detection of a 40% intervention-induced difference in the development of autoantibodies and subsequent diabetes, the study requires 2032 subjects. A multicenter, international, collaborative effort is necessary to achieve recruitment targets. A collaborative international study group of 78 clinical centers in 15 countries has therefore been assembled for this purpose.

  • 33.
    Tercyak, Kenneth P
    et al.
    Georgetown University, DC 20007 USA .
    Mays, Darren
    Georgetown University, DC 20007 USA .
    Bennett Johnson, Suzanne
    Florida State University, FL 32306 USA .
    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.
    Swartling, Ulrica
    Lund University, Sweden .
    Psychometric properties of the Pediatric Testing Attitudes Scale-Diabetes (P-TAS-D) for parents of children undergoing predictive risk screening2013In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, no 8, p. 602-610Article in journal (Refereed)
    Abstract [en]

    ObjectiveExamine the factor structure, reliability, and validity of the Pediatric Testing Attitudes Scale-Diabetes (P-TAS-D), a measure of parental attitudes about predictive risk screening for type 1 diabetes in children. less thanbrgreater than less thanbrgreater thanMethodsSurveys were completed by 3720 Swedish parents of children participating in the adolescent follow-up of a birth cohort study of type 1 diabetes onset. Parents averaged 43.5years, 42.3% were college-educated, and 10.6% of children had a family history of type 1 diabetes. The parent sample was randomly divided, an exploratory factor analysis (EFA; n =1860) was conducted, followed by confirmatory factor analysis (CFA; n =1860) and testing. less thanbrgreater than less thanbrgreater thanResultsEFA/CFA revealed the P-TAS-D has three factors/scales: Attitudes and Beliefs toward type 1 diabetes predictive risk screening (=0.92), Communication about risk screening results (=0.71), and Decision Making (r = 0.19, pandlt;0.001). This solution fit the data well ((2) [42]=536.0, RMSEA = 0.08, CFI = 0.95) and internal consistency for the full scale was high (=0.86, M = 36.2, SD = 8.2). After adjusting for covariates, more favorable attitudes toward childrens risk screening were associated with greater worry about type 1 diabetes (B = 1.1, p andlt;0.001), less worry about health overall (B = -0.10, p = 0.001), and more positive attitudes toward (B = 0.28, p andlt;0.001) and less worry about (B = 0.41, p andlt;0.001) diabetes research. less thanbrgreater than less thanbrgreater thanConclusionsThe P-TAS-D is a stable, reliable, and valid measure for assessing parents type 1 diabetes risk screening attitudes. Scale data can help target parent education efforts in risk screening trials.

  • 34. Vrabelova, Z
    et al.
    Kolouskova, S
    Böhmova, K
    Faresjö, Maria
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Pediatrics.
    Sumnik, Z
    Pechova, M
    Kverka, M
    Chudoba, D
    Zacharovova, K
    Stadlerova, G
    Pithova, P
    Hladikova, M
    Stechova, K
    Protein microarray analysis as a tool for monitoring cellular autoreactivity in type 1 diabetes patients and their relatives2007In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 8, no 5, p. 252-260Article in journal (Refereed)
    Abstract [en]

    Background: Autoreactive T cells have a crucial role in type 1 diabetes (T1D) pathogenesis.: Objectives: The aim of our study was to monitor the in vitro production of cytokines by peripheral blood mononuclear cells (PBMCs) after stimulation with diabetogenic autoantigens. Subjects: Ten T1D patients (tested at the time of diagnosis and 6 and 12 months later), 10 first-degree relatives of the T1D patients, and 10 controls underwent the study. Methods: PBMCs were stimulated with glutamic acid decarboxylase 65 (GAD65) amino acids (a.a.) 247-279, 509-528, and 524-543, proinsulin a.a. 9-23, and tyrosine phosphatase (islet antigen-2)/R2 a.a. 853-872. Interleukin (IL)-2, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-γ, tumor necrosis factor β, transforming growth factor β1, and granulocyte colony-stimulating factor (GCSF) were analyzed by protein microarray. Results: Differences in cytokine(s) poststimulatory and mainly in basal production were observed in all groups. The most prominent findings were in controls, the higher basal levels of IL-2, IL-4, IL-5, IL-13, and GCSF were observed when compared with relatives (p < 0.05, for all). After stimulation in controls, there was a significant decrease in IL-2, IL-13, GCSF, and IFN-γ (p < 0.05, for all). The group of relatives was the most variable in poststimulatory production. A strong correlation between cytokines production was found but groups differed in this aspect. Conclusion: By multiplex analysis, it may be possible, for example, to define the risk immunological response pattern among relatives or to monitor the immune response in patients on immune modulation therapy. © 2007 The Authors Journal compilation © 2007 Blackwell Munksgaard.

  • 35.
    Wahlberg, Jeanette
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Fredriksson (Walldén), Jenny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Nikolic, Elisabet
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Vaarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Environmental factors related to the induction of beta-cell autoantibodies in 1-yr-old healthy children2005In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 6, no 4, p. 199-205Article in journal (Refereed)
    Abstract [en]

    We studied environmental risk factors which might contribute to the development of beta-cell autoantibodies in healthy children. Here, we investigated 6000 randomly selected children from the large All Babies in Southeast Sweden (ABIS) cohort, including 17 055 newborns recruited between 1997 and 1999. Questionnaires at birth and at 1 yr of age and the levels of autoantibodies to glutamic acid decarboxylase (GADA) and autoantibodies to tyrosine phosphatase (IA-2A) at 1 yr of age were analyzed. The 99th percentile cutoff for autoantibodies was proposed to identify children at risk of type 1 diabetes (T1D) and the 90th percentile cutoff to identify children in whom beta-cell autoimmunity has been induced. Using the 90th percentile cutoff level, 1156 children had either IA-2A (n = 574) or GADA (n = 582), while 126 children had both GADA and IA-2A. When the 99th percentile cutoff level was used, 114 children had either IA-2A (n = 57) or GADA (n = 57), and six children had both GADA and IA-2A. In logistic regression analysis, celiac disease in grandparents [odds ratio (OR) 2.2] and maternal gastrointestinal infection (OR 1.1) represented a risk for simultaneous occurrence of both IA-2A and GADA above the 90th percentile. Birth in spring (March to May) (OR 1.5) and male gender (OR 1.3) were risk factors for induction of IA-2A. Mother's low education represented a risk for induction of IA-2A (OR 1.5) and GADA (OR 1.4). T1D in first-degree relatives increased the risk for beta-cell autoimmunity above the 99th percentile (OR 2.6), whereas type 2 diabetes in grandparents was associated with GADA (OR 2.1). Exposure to cow's milk formulas <2 months of age implied an OR of 2.9 for IA-2A above the 99th percentile.

  • 36.
    Wahlberg, Jeanette
    et al.
    Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology and Gastroenterology UHL.
    Waarala, Outi
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Ludvigsson, Johnny
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
    Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children2011In: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 12, no 7, p. 604-610Article in journal (Refereed)
    Abstract [en]

    A dominance of Th2 cytokine pattern is associated with allergic diseases, whereas a Th1 pattern has been reported in autoimmune type 1 diabetes (T1D). The Th1/Th2 paradigm has led to the interest in the relationship between these diseases. To investigate the association between atopic diseases, asthma and occurrence of T1D-related β-cell autoantibodies in children, we studied 7208 unselected 2.5-yr-old children from the All Babies in Southeast Sweden (ABIS) cohort. The ABIS cohort includes 17 055 (78.3% out of all 21 700) children born from October 1997 to October 1999, and followed prospectively with regular biological samples and questionnaires, at birth, at 1 and 2.5 yr. Risk factors for development of β-cell autoantibodies at the age of 2.5 yr were type of domiciliary, domestic animals (cat and dog) and getting a new brother/sister during first year of life. Maternal smoking during pregnancy [odds ratio (OR) 1.6] and heavy smoking at home (>10 vs. ≤10 cigarettes) implied risk for tyrosine phosphatase autoantibodies (IA-2A) (OR 2.9). Wheezing during the first year of life implied risk for glutamic acid decarboxylase autoantibodies (GADA) (OR 1.9) and double positivity for GADA and IA-2A (OR 9.1). Rash on several locations (at least three times during 12 months) (OR 1.7) as well as allergic symptoms related to fur-bearing animals (OR 2.7) implied risk for IA-2A. Food allergy against egg, cow-milk, fish, nuts/almonds (one or in combination) implied risk for GADA and IA-2A (OR 4.5). In a regression model wheezing during first year of life remained as a risk factor for GADA [OR 2.0, confidence interval (CI) 1.1–3.8; p = 0.031] and both GADA and IA-2A (OR 10.7, CI 3.9–29.4; p = 0.000). We conclude that allergic symptoms are associated with the development of T1D-related autoantibodies during the first years of life.

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