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  • 1. Andersson, C
    et al.
    Vaziri-Sani, F
    Delli, Aj
    Lindblad, B
    Carlsson, A
    Forsander, G
    Ludvigsson, J
    Marcus, C
    Samuelsson, U
    Ivarsson, Sa
    Lernmark, A
    Larsson, H Elding
    Triple specificity of ZnT8 autoantibodies in relation to HLA and other islet autoantibodies in childhood and adolescent type 1 diabetes.2013Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, nr 2, s. 97-105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    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 1-3 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 (p < 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.

  • 2.
    Andersson, Cecilia
    et al.
    Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmö, Sweden.
    Carlsson, Annelie
    Department of Paediatrics, Lund University, Skåne University Hospital SUS, Lund, Sweden.
    Cilio, Corrado
    Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmö, Sweden.
    Cedervall, Elisabeth
    Department of Paediatrics, Helsingborg Hospital, Helsingborg, Sweden.
    Ivarsson, Sten-Anders
    Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmö, Sweden.
    Jonsdottir, Berglind
    Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmö, Sweden.
    Jönsson, Björn
    Department of Paediatrics, Ystad Hospital, Ystad, Sweden.
    Larsson, Karin
    Department of Paediatrics, Kristianstad Hospital, Kristianstad, Sweden.
    Neiderud, Jan
    Department of Paediatrics, Helsingborg Hospital, Helsingborg, Sweden.
    Lernmark, Åke
    Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmö, Sweden.
    Elding Larsson, Helena
    Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmö, Sweden.
    Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study2013Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 14, nr 5, s. 341-349Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children.

    METHODS: In 47 healthy children with GADA and at least one additional islet autoantibody, intravenous glucose tolerance test (IvGTT) and oral glucose tolerance test (OGTT) were performed 8-65 d apart. Hemoglobin A1c, plasma glucose as well as serum insulin and C-peptide were determined at fasting and during IvGTT and OGTT.

    RESULTS: All children aged median 5.1 (4.0-9.2) yr had autoantibodies to two to six of the beta-cell antigens GAD65, insulin, IA-2, and the three amino acid position 325 variants of the ZnT8 transporter. In total, 20/47 children showed impaired glucose metabolism. Decreased (≤ 30 μU/mL insulin) first-phase insulin response (FPIR) was found in 14/20 children while 11/20 had impaired glucose tolerance in the OGTT. Five children had both impaired glucose tolerance and FPIR ≤ 30 μU/mL insulin. Number and levels of autoantibodies were not associated with glucose metabolism, except for an increased frequency (p = 0.03) and level (p = 0.01) of ZnT8QA in children with impaired glucose metabolism. Among the children with impaired glucose metabolism, 13/20 had HLA-DQ2/8, compared to 9/27 of the children with normal glucose metabolism (p = 0.03).

    CONCLUSION: Secondary prevention studies in children with islet autoantibodies are complicated by variability in baseline glucose metabolism. Evaluation of metabolic control with both IvGTT and OGTT is critical and should be taken into account before randomization. All currently available autoantibody tests should be analyzed, including ZnT8QA.

  • 3.
    Bratina, Natasa
    et al.
    Univ Childrens Hosp, Dept Endocrinol Diabet & Metab, Ljubljana, Slovenia.
    Forsander, Gun
    Queen Silvia Childrens Hosp, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg, Sweden.
    Annan, Francesca
    Univ Coll London Hosp NHS Trust, London, England.
    Wysocki, Tim
    Nemours Children Hlth Syst, Ctr Healthcare Delivery Sci, Orlando, FL USA.
    Pierce, Jessica
    Nemours Children Hlth Syst, Ctr Healthcare Delivery Sci, Orlando, FL USA.
    Calliari, Luis E.
    Santa Casa Sao Paulo Sch Med Sci, Dept Pediat, Sao Paulo, Brazil.
    Pacaud, Daniele
    Univ Calgary, Alberta Childrens Hosp, Div Diabet & Endocrinol, Dept Paediat, Calgary, AB, Canada.
    Adolfsson, Peter
    Hosp Halland, Dept Pediat, Kungsbacka, Sweden.
    Dovc, Klemen
    Univ Childrens Hosp, Dept Endocrinol Diabet & Metab, Ljubljana, Slovenia.
    Middlehurst, Angie
    Int Diabet Federat Life Child Program, Sydney, NSW, Australia.
    Goss, Peter
    Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Gothenburg, Sweden;Team Diabet, Geelong, Vic, Australia.
    Goss, Jennifer
    Team Diabet, Geelong, Vic, Australia.
    Janson, Staffan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Acerini, Carlo L.
    Univ Cambridge, Dept Paediat, Cambridge, England.
    ISPAD Clinical Practice Consensus Guidelines 2018: Management and support of children and adolescents with type 1 diabetes in school2018Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, s. 287-301Artikel i tidskrift (Refereegranskat)
  • 4.
    Brorsson, Anna Lena
    et al.
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden;Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Leksell, Janeth
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Dalarna Univ, Sch Educ Hlth & Social Studies, Falun, Sweden.
    Franko, Mikael Andersson
    Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Olinder, Anna Lindholm
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism. Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    A person-centered education for adolescents with type 1 diabetes: A randomized controlled trial2019Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, nr 7, s. 986-996Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Young people with type 1 diabetes and their parents need to receive person-centered education to be able to manage their diabetes. Guided Self-Determination-Young (GSD-Y) is a person-centered communication and reflection education model that can be used in educational program for young people with type 1 diabetes.

    Objective: To evaluate whether GSD-Y leads to improved glycaemic control, increased self-perceived health and health-related quality of life, fewer diabetes-related family conflicts, and improved self-efficacy in a group-based intervention for adolescents starting continuous subcutaneous insulin infusion (CSII) and their parents.

    Methods: This randomized controlled trial included 71 adolescents starting CSII. Participants were followed for 12 months. The intervention group (n = 37) attended seven group training sessions over a period of 5 months, using the GSD-Y model, the control group received standard care. Variables evaluated were HbA1c, self-perceived health, health-related quality of life, family conflicts, self-efficacy, and usage of continuous glucose monitoring.

    Results: When adjusted for sex and family conflicts, there was a difference in glycaemic control between the groups at 12 months, favoring the intervention group (62 vs 70 mmol/mol, P = .009). When analyses were performed on boys and girls separately and adjusted for family conflicts, the only difference detected was for boys after 12 months (P = .019). The intervention showed no effect on self-perceived health, health-related related quality of life, family conflicts, or self-efficacy.

    Conclusions: An intervention with GSD-Y may have an effect on glycaemic control. The content of the GSD-Y groups may serve as a model for person-centered care in adolescents with type 1 diabetes.

  • 5.
    Brorsson, Anna Lena
    et al.
    Karolinska Institutet.
    Viklund, Gunnel
    Karolinska Institutet.
    Örtqvist, Eva
    Karolinska Institutet.
    Lindholm Olinder, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk diabetologi och metabolism.
    Does treatment with an insulin pump improve glycaemic control in children and adolescents with type 1 diabetes?: A retrospective case-control study2014Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 16, nr 7, s. 546-553Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate long-term effects on glycaemic control, ketoacidosis, serious hypoglycaemic events, insulin requirements, and body mass index standard deviation scores (BMI-SDS) in children and adolescents with type 1 diabetes starting on continuous subcutaneous insulin infusion (CSII) compared with children and adolescents treated with multiple daily injections (MDI).

    METHODS: This retrospective case-control study compares 216 patients starting CSII with a control group on MDI (n = 215), matched for glycated hemoglobin (HbA1c), sex, and age during a 2-yr period. Variables collected were gender, age, HbA1c, insulin requirement, BMI, BMI-SDS, ketoacidosis, and serious hypoglycaemic events.

    RESULTS: In the CSII group there was an improvement in HbA1c after 6 and 12 months compared with the MDI group. For boys and girls separately the same effect was detected after 6 months, but only for boys after 12 months. The incidence of ketoacidosis was higher in the CSII group compared with the MDI group (2.8 vs. 0.5/100 person-yr). The incidences of severe hypoglycaemic episodes per 100 person-yr were three in the CSII group and six in the MDI group (p < 0.05). After 6, 12, and 24 months, the insulin requirement was higher in the MDI group.

    CONCLUSIONS: This study shows that treatment with CSII resulted in an improvement in HbA1c levels up to 1 yr and decreased the number of severe hypoglycaemic events, but the frequency of ketoacidosis increased. The major challenge is to identify methods to maintain the HbA1c improvement, especially among older children and teenagers, and reduce the frequency of ketoacidosis.

  • 6.
    Chiavaroli, Valentina
    et al.
    Univ Auckland, Liggins Inst, Auckland, New Zealand;Pescara Publ Hosp, Neonatal Intens Care Unit, Pescara, Italy.
    Derraik, Jose G. B.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Univ Auckland, Liggins Inst, Auckland, New Zealand;Univ Auckland, A Better Start Natl Sci Challenge, Auckland, New Zealand.
    Jalaludin, Muhammad Y.
    Univ Auckland, Liggins Inst, Auckland, New Zealand;Univ Malaya, Fac Med, Kuala Lumpur, Malaysia.
    Albert, Benjamin B.
    Univ Auckland, Liggins Inst, Auckland, New Zealand;Auckland Dist Hlth Board, Starship Childrens Hlth, Auckland, New Zealand.
    Ramkumar, Selvarajan
    Apollo Hosp, Dept Endocrinol, Chennai, Tamil Nadu, India;Madras Med Coll & Govt Gen Hosp, Dept Endocrinol, Chennai, Tamil Nadu, India.
    Cutfield, Wayne S.
    Univ Auckland, Liggins Inst, Auckland, New Zealand;Univ Auckland, A Better Start Natl Sci Challenge, Auckland, New Zealand;Auckland Dist Hlth Board, Starship Childrens Hlth, Auckland, New Zealand.
    Hofman, Paul L.
    Univ Auckland, Liggins Inst, Auckland, New Zealand;Auckland Dist Hlth Board, Starship Childrens Hlth, Auckland, New Zealand.
    Jefferies, Craig A.
    Univ Auckland, Liggins Inst, Auckland, New Zealand;Auckland Dist Hlth Board, Starship Childrens Hlth, Auckland, New Zealand.
    Partial remission in type 1 diabetes and associated factors: Analysis based on the insulin dose-adjusted hemoglobin A1c in children and adolescents from a regional diabetes center, Auckland, New Zealand2019Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, nr 7, s. 892-900Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Partial remission (PREM) by the insulin dose-adjusted HbA1c (IDAA1c) method has not been evaluated for the combined associations of ethnicity and socioeconomic status in children and adolescents with type 1 diabetes (T1D). Objective To investigate prevalence and predictors of PREM defined by IDAA1c. Methods Six hundred fourteen of 678 children (aged <15 years) with new-onset T1D (2000-2013) from a regional pediatric diabetes service (Auckland, New Zealand). Results Overall rate of PREM at 3 months was 42.4%, and lower in Maori/Pacific children (28.6%; P = .006) and those of other ethnicities (28.8%; P = .030) compared with New Zealand Europeans (50.4%). Comparing the most and least deprived socioeconomic quintiles, the odds of PREM were lower among the most deprived (adjusted odds ratio [aOR] 0.44; P = .019). Lower rates of PREM were seen in children aged 0 to 4.9 years (23.8%) and 10 to 14 years (40.9%) than in children aged 5 to 9.9 years (57.4%; P < .05). Further predictors of lower rates of PREM were ketoacidosis at diagnosis (aOR 0.54 with DKA; P = .002) and diabetes duration (aOR 0.84 per month; P < .0001). Patient's sex, body mass index standard deviation score, or autoantibodies were not associated with PREM. PREM at 3 months was associated with lower HbA1c over 18 months compared with children not in PREM (65.0 vs 71.3 mmol/mol; P < .0001), independent of ketoacidosis. Conclusions This study on a regional cohort of youth with T1D showed social and ethnic disparities in rates of PREM defined by IDAA1c. Further research into reducing ketoacidosis rates at diagnosis and addressing factors associated with lower rates of PREM in non-European children are important health priorities.

  • 7.
    Derraik, Jose G. B.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Univ Auckland, Liggins Inst, Private Bag 92019, Auckland 1023, New Zealand.;Univ Auckland, Better Start Natl Sci Challenge, Auckland, New Zealand..
    Cutfield, Wayne S.
    Univ Auckland, Liggins Inst, Private Bag 92019, Auckland 1023, New Zealand.;Univ Auckland, Better Start Natl Sci Challenge, Auckland, New Zealand.;Auckland Dist Hlth Board, Starship Childrens Hlth, Auckland, New Zealand..
    Maessen, Sarah E.
    Univ Auckland, Liggins Inst, Private Bag 92019, Auckland 1023, New Zealand..
    Hofman, Paul L.
    Univ Auckland, Liggins Inst, Private Bag 92019, Auckland 1023, New Zealand.;Auckland Dist Hlth Board, Starship Childrens Hlth, Auckland, New Zealand..
    Kenealy, Timothy
    Univ Auckland, Liggins Inst, Private Bag 92019, Auckland 1023, New Zealand.;Univ Auckland, Sch Med, Fac Med & Hlth Sci, Auckland, New Zealand..
    Gunn, Alistair J.
    Auckland Dist Hlth Board, Starship Childrens Hlth, Auckland, New Zealand.;Univ Auckland, Dept Physiol, Auckland, New Zealand..
    Jefferies, Craig A.
    Univ Auckland, Liggins Inst, Private Bag 92019, Auckland 1023, New Zealand.;Auckland Dist Hlth Board, Starship Childrens Hlth, Auckland, New Zealand..
    A brief campaign to prevent diabetic ketoacidosis in children newly diagnosed with type 1 diabetes mellitus: The NO-DKA Study2018Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, nr 7, s. 1257-1262Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective New-onset diabetic ketoacidosis (NO-DKA) is entirely preventable with early recognition of the symptoms of type 1 diabetes mellitus (T1D). In this study, we aimed to assess whether a simple and easily delivered educational campaign could reduce the risk of DKA. Methods A poster highlighting key features of new-onset T1D was delivered once a year over 2 years to mailboxes of over 460000 individual residential households in the Auckland region (New Zealand). In the first year, the campaign poster was also delivered to all general practices in the region. Families of all newly diagnosed cases of T1D in children answered a brief questionnaire to ascertain whether the campaign reached them. Results Over the 24-month period covered by this study, 132 new cases of T1D were diagnosed in children and adolescents in Auckland. There were 38 cases (28.8%) of DKA, which is similar to the average over the previous 5-year period (27.0%). The caregivers of three children reported both seeing the campaign poster and seeking medical attention as a result. None of these three children were in DKA at diagnosis; they were aged 6.3 to 9.7 years, and of New Zealand European ethnicity. Conclusions A non-targeted campaign to raise awareness of diabetes symptoms in youth led only a few caregivers to seek timely medical attention. Overall, this once-yearly untargeted campaign to raise awareness of diabetes symptoms in youth had limited impact. More effective strategies are required, possibly involving sustained targeted education of medical practitioners.

  • 8. Helgesson, Gert
    et al.
    Hansson, Mats G
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Enheten för biomedicinsk etik.
    Ludvigsson, Johnny
    Swartling, Ulrica
    Practical matters, rather than lack of trust, motivate non-participation in a long-term cohort trial2009Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 10, nr 6, s. 408-412Artikel i tidskrift (Refereegranskat)
    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.

  • 9.
    Hjern, Anders
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Söderström, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i D län (CKFD).
    Parental country of birth is a major determinant of childhood type 1 diabetes in Sweden2008Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, nr 1, s. 35-39Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To test the hypothesis that the risk of childhood diabetes type 1 increases with migration from a low to a high incidence region. METHODS: Register study of a national cohort of 783 547 children born between 1987 and 1993 who remained in Sweden in 2002, including 3225 children with childhood type 1 diabetes identified in hospital discharge data. Logistic regression analysis was used to test the hypotheses. RESULTS: Offspring of two parents born in very low (Asia excluding Middle East and Latin America) and low (southern and eastern Europe and the Middle East) incidence regions had the lowest adjusted odds ratios (ORs) of childhood type 1 diabetes; 0.21 (0.11-0.41) and 0.37 (0.29-0.48), respectively, compared with the Swedish majority population. When one parent was born in a low incidence country and one parent was Swedish born, the adjusted ORs increased but remained lower than the Swedish majority population. CONCLUSIONS: Parental country of birth is an important determinant of childhood type 1 in Sweden. Heritable factors seem most likely to explain this pattern.

  • 10. Larsson, Karin
    et al.
    Carlsson, Annelie
    Cederwall, Elisabeth
    Jonsson, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Neiderud, Jan
    Jonsson, Bjorn
    Lernmark, Ake
    Ivarsson, Sten A.
    Annual screening detects celiac disease in children with type 1 diabetes2008Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 9, nr 4, s. 354-359Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate the prevalence of celiac disease (CD) in a cohort of type 1 diabetes mellitus (T1DM) children and adolescents at the time of clinical diagnosis and to evaluate the screening procedure and possible role of human leukocyte antigen (HLA)-DQ during a 5-yr follow-up. Research design and methods: The study group was a cohort of 300 newly diagnosed T1DM children and youths younger than 20 yr followed for 5 yr at six clinical centers for pediatric diabetes in the region Skane in Sweden. Immunoglobulin A endomysium antibodies were used to screen the patients annually to be considered for an intestinal biopsy. All patients were analyzed for HLA-DQA1-B1 genotypes. Results: While 0.7% (2/300) already had a diagnosed symptomatic CD, an additional 3% (10/300) had silent CD at the diagnosis of T1DM. During follow-up, another 6% (17/300) developed CD as follows: 10 after 1 yr, 5 after 2 yr, 1 after 3 yr, and 1 after 5 yr. Therefore, the cumulative frequency of CD confirmed by intestinal biopsies was 10% (29/300). HLA genotypes among T1DM patients developing CD were not different from those among patients with T1DM alone. Conclusions: Our study confirmed the low prevalence (0.7%) of diagnosed symptomatic CD at the time of clinical diagnosis but document by screening an increasing prevalence of silent CD during a 5-yr follow-up to reach an overall prevalence of 10%. We suggest that children with T1DM should be screened for CD at the onset of T1DM and annually for a minimum of at least 2 yr. HLA genotypes among T1DM patients developing CD were not different from those among patients with T1DM alone.

  • 11.
    Lindholm Olinder, Anna
    et al.
    Sachs’ Children Hospital, Södersjukhuset, Stockholm, Sweden.
    Kernell, Anna
    Smide, Bibbi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Treatment with CSII in two infants with neonatal diabetes mellitus2006Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 7, nr 5, s. 284-288Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This article reports the case studies of two children with neonatal onset of diabetes who were treated with continuous subcutaneous insulin infusion (CSII) from within 4 d to 3 wk of the diagnosis. The aim was to describe diabetes-related and insulin-pump-specific data in relation to growth and various feeding patterns when using CSII in infants with diabetes during their first year of life. The two children’s medical records were scrutinized. The results showed that both children had good metabolic control [median hemoglobin A1c (HbA1c) 5.3 and 5.7%, high performance liquid chromatography (HPLC) method, reference: 3.4–5.0%. Compared with the Diabetes Control and Complications Trial (DCCT) HbA1c units, Swedish units give approximately 1% point lower results]. No episodes of severe hypoglycemia or diabetic ketoacidosis have been demonstrated. The children had normal growth patterns, as they followed a normal feeding regime for their age. The meal doses of insulin were given over 12 min to 3 h. The children had diluted Humalog® insulin 10 U/mL (Eli Lilly & Co, Indianapolis, IN, USA) in their pumps. Different types of insulin pumps were used, namely, the Minimed 507C and 508 (Medtronic, Minneapolis, MN, USA), and a Disetronic H-tron V100 (Roche Diagnostics, Basel, Switzerland). The children used different types of infusion sets. Neither family reported any technical problems with their pump system. CSII was an effective and safe treatment for the two children suffering from neonatal diabetes. This offers an alternative for other infants with a similar diagnosis.

  • 12.
    Lindholm Olinder, Anna
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Ternulf Nyhlin, Kerstin
    University of Skövde, School of Life Sciences.
    Smide, Bibbi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Reasons for missed meal-time insulin boluses, from the perspective of adolescents using insulin pumps – “lost focus”2011Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 12, nr 4, s. 402-409Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To investigate the reasons for missed bolus doses and strategies for avoiding this among adolescents using insulin pumps.

    Methods: The grounded theory method was chosen as a model for the collection and analysis of data. Data were collected through interviews with 12 adolescents treated with an insulin pump (5 males and 7 females, mean age 14.4 yr) from different Swedish pediatric diabetes clinics. All interviews were tape-recorded and immediately transcribed.

    Results: The core category 'lost focus' emerged as representing the main reason for missed bolus doses. Identified subcategories were delayed lost focus, directly lost focus, and totally lost focus. There was a risk of delayed lost focus when the adolescent used postprandial bolusing. Focus could also be lost directly in connection with the start of the meal. Totally lost focus could occur when the adolescent perceived the impact of diabetes as too high or tried to neglect that he or she had it. The category 'agreements about reminders' appeared to be the main strategy for avoiding missed bolus doses; subcategories were personal reminders and technical reminders. The adolescent needed to be involved in these agreements; otherwise, the reminding could be seen as nagging and did not work.

    Conclusion: The results may help diabetes care teams understand the circumstances in which adolescents miss their bolus doses. This understanding may make it easier to discuss missed doses and strategies for avoiding this with adolescents and support negotiations over agreements about reminders between them and their parents.

  • 13. Lindholm-Olinder, Anna
    et al.
    Kernell, Anna
    Smide, Bibbi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Treatment with CSII in two infants with neonatal diabetes mellitus2006Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 7, nr 5, s. 284-288Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This article reports the case studies of two children with neonatal onset of diabetes who were treated with continuous subcutaneous insulin infusion (CSII) from within 4 d to 3 wk of the diagnosis. The aim was to describe diabetes-related and insulin-pump-specific data in relation to growth and various feeding patterns when using CSII in infants with diabetes during their first year of life. The two children's medical records were scrutinized. The results showed that both children had good metabolic control [median hemoglobin A1c (HbA1c) 5.3 and 5.7%, high performance liquid chromatography (HPLC) method, reference: 3.4-5.0%. Compared with the Diabetes Control and Complications Trial (DCCT) HbA1c units, Swedish units give approximately 1% point lower results]. No episodes of severe hypoglycemia or diabetic ketoacidosis have been demonstrated. The children had normal growth patterns, as they followed a normal feeding regime for their age. The meal doses of insulin were given over 12 min to 3 h. The children had diluted Humalog((R)) insulin 10 U/mL (Eli Lilly & Co, Indianapolis, IN, USA) in their pumps. Different types of insulin pumps were used, namely, the Minimed 507C and 508 (Medtronic, Minneapolis, MN, USA), and a Disetronic H-tron V100 (Roche Diagnostics, Basel, Switzerland). The children used different types of infusion sets. Neither family reported any technical problems with their pump system. CSII was an effective and safe treatment for the two children suffering from neonatal diabetes. This offers an alternative for other infants with a similar diagnosis.

  • 14.
    Manell, Hannes
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Kristinsson, Hjalti
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Kullberg, Joel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Ubhayasekera, Sarojini Jayantha Kumari
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Mörwald, Katharina
    Paracelsus Medical University.
    Staaf, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Cadamuro, Janne
    Paracelsus Medical University.
    Zsoldos, Fanni
    Paracelsus Medical University.
    Göpel, Sven
    AstraZeneca.
    Sargsyan, Ernest
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
    Ahlström, Håkan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Radiologi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för kemi - BMC, Analytisk kemi.
    Weghuber, Daniel
    Paracelsus Medical University.
    Forslund, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Bergsten, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Hyperglucagonemia in youth is associated with high plasma free fatty acids, visceral adiposity and impaired glucose tolerance2019Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 20, nr 7, s. 880-891Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To delineate mechanisms for fasting hyperglucagonemia in childhood obesity bystudying the associations between fasting plasma glucagon concentrations and plasmalipid parameters and fat compartments.

    Methods: Cross-sectional study of children and adolescents with obesity (n=147) and leancontrols (n=43). Differences in free fatty acids (FFA), triglycerides, insulin and fatcompartments (quantified by magnetic resonance imaging) across quartiles of fastingplasma glucagon concentration were analysed. Differences in OGTT glucagonresponse was tested in high vs low FFAs, triglycerides and insulin. Human islets ofLangerhans were cultured at 5.5 mmol/l glucose and in the absence or presence of aFFA mixture with total FFA concentration of 0.5 mmol/l and glucagon secretionquantified.

    Results: In children with obesity, the quartile with the highest fasting glucagon had higherinsulin (201±174 vs 83±39 pmol/l, p<0.01), FFAs (383±52 vs 338±109 μmol/l,p=0.02), triglycerides (1.5±0.9 vs 1.0±0.7 mmol/l, p<0.01), visceral adipose tissuevolume (1.9±0.8 vs 1.2±0.3 dm3, p<0.001) and a higher prevalence of impairedglucose tolerance (41% vs 8%, p=0.01) than the lowest quartile. During OGTT,children with obesity and high insulin had a worse suppression of glucagon during thefirst 10 minutes after glucose intake. Glucagon secretion was 2.6-fold higher in isletstreated with FFAs than in those not treated with FFAs.4

    Conclusion: Hyperglucagonemia in childhood obesity is associated with hyperinsulinemia, highplasma FFAs, high plasma triglycerides, visceral adiposity and impaired glucosetolerance. The glucagonotropic effect of FFAs on isolated human islets provides apotential mechanism linking high fasting plasma FFAs and glucagon levels.

  • 15.
    Nylander, Charlotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnendokrinologisk forskning. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Lindstrom, K.
    Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Dept Neuropaediat, Stockholm, Sweden.
    Khalifa, Najah
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Barn- och ungdomspsykiatri. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg.
    Fernell, E.
    Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden.
    Previously undiagnosed attention-deficit/hyperactivity disorder associated with poor metabolic control in adolescents with type 1 diabetes2018Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, nr 4, s. 816-822Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Managing modern diabetes treatment requires efficient executive functions. Patients with attention-deficit/hyperactivity disorder (ADHD) and type 1 diabetes have poor metabolic control and present with ketoacidosis more often than patients without ADHD. Objective: To assess whether patients with type 1 diabetes and with indications of executive problems met criteria for ADHD, and to investigate whether these patients had difficulties achieving metabolic control. Methods: In a hospital-based study, including 3 pediatric departments at hospitals in Stockholm and Uppsala, Sweden, questionnaires regarding executive problems had been filled out by 12- to 18-year-old patients with type 1 diabetes and their parents. Out of 166 patients with completed questionnaires, 49 were selected for a clinical study due to reported executive problems/ADHD symptoms. However, 7 already had a diagnosis of ADHD, 21 denied follow-up, 8 did not respond, leaving 13 adolescents for the clinical assessment. Results: Of the clinically assessed adolescents, 9 (6 girls) met criteria for ADHD. Patients who did not respond to the follow-up and patients who were diagnosed with ADHD within the study, showed to a larger extent than the other study groups high HbA1c levels (>70 mmol/mol, 8,6%). HbA1c >70 mmol/mol (8.6%) was associated with diagnosed ADHD (prior to or within the study), odds ratio 2.96 (95% confidence interval 1.02-8.60). Conclusion: Patients with type 1 diabetes and poor metabolic control should be assessed with regard to ADHD. There is a need for paying special attention to girls with poor metabolic control.

  • 16.
    Nylander, Charlotte
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnendokrinologisk forskning.
    Tindberg, Ylva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Haas, Josephine
    Swenne, Ingemar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnendokrinologisk forskning.
    Torbjörnsdotter, Torun
    Åkesson, Karin
    Örtqvist, Eva
    Gustafsson, Jan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Barnendokrinologisk forskning.
    Fernell, Elisabeth
    Self- and parent-reported executive problems in adolescents with type 1 diabetes are associated with poor metabolic control and low physical activity.2018Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 19, nr 1, s. 98-105Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Management of diabetes is demanding and requires efficient cognitive skills, especially in the domain of executive functioning. However, the impact of impaired executive functions on diabetes control has been studied to a limited extent. The aim of the study is to investigate the association between executive problems and diabetes control in adolescents with type 1 diabetes.

    MATERIALS AND METHODS: Two hundred and forty-one of 477 (51%) of 12- to 18-year-old adolescents, with a diabetes duration of >2 years in Stockholm, Uppsala, and Jönköping participated. Parents and adolescents completed questionnaires, including Behavioral Rating Inventory of Executive Function (BRIEF), Attention-Deficit/Hyperactivity Disorder (ADHD)-Rating Scale (ADHD-RS) and demographic background factors. Diabetes-related data were collected from the Swedish Childhood Diabetes Registry, SWEDIABKIDS. Self-rated and parent-rated executive problems were analyzed with regard to gender, glycosylated hemoglobin (HbA1c), frequency of outpatient visits, and physical activity, using chi-square tests or Fisher's test, where P-values <.05 were considered significant. Furthermore, adjusted logistic regressions were performed with executive problems as independent variable.

    RESULTS: Executive problems, according to BRIEF and/or ADHD-RS were for both genders associated with mean HbA1c >70 mmol/mol (patient rating P = .000, parent rating P = .017), a large number of outpatient visits (parent rating P = .015), and low physical activity (patient rating P = .000, parent rating P = .025). Self-rated executive problems were more prevalent in girls (P = .032), while parents reported these problems to a larger extent in boys (P = .028).

    CONCLUSION: Executive problems are related to poor metabolic control in adolescents with type 1 diabetes. Patients with executive problems need to be recognized by the diabetes team and the diabetes care should be organized to provide adequate support for these patients.

  • 17.
    Olinder, Anna Lindholm
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kernell, Anna
    Karolinska Institutet.
    Smide, Bibbi
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Missed bolus doses: devastating for metabolic control in CSII-treated adolescents with type 1 diabetes2009Ingår i: Pediatric Diabetes, ISSN 1399-543X, E-ISSN 1399-5448, Vol. 10, nr 2, s. 142-148Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To investigate the management of continuous subcutaneous insulin infusion (CSII) in adolescents with type 1 diabetes including their administration of bolus doses and to study relationships between insulin omission and metabolic control, body mass index, daily frequency of self-monitoring of blood glucose (SMBG) and bolus doses, health-related quality of life (HRQOL), the burden of diabetes and treatment satisfaction. METHODS: Ninety CSII-treated (> or =6 months) adolescents aged 12-18 yr, from four diabetes clinics in Sweden, participated in the study. The adolescents recorded their meal intake the previous day, which was compared with downloaded pump data, and the frequency of missed boluses was stated. Haemoglobin A1c (HbA1c) and diabetes-related data were recorded. HRQOL and treatment satisfaction were measured with questionnaires. RESULTS: Thirty-eight per cent of the adolescents had missed >15% of the doses the previous day, those had higher HbA1c (7.8 +/- 1.0 vs. 7.0 +/- 1.2%, p = 0.001), took fewer daily boluses (3.8 +/- 1.7 vs. 5.3 +/- 1.7, p < 0.001) and SMBG (2.4 +/- 1.8 vs. 3.6 +/- 1.8, p = 0.003), were less satisfied with their treatment (4.8 vs. 5.3, scale 0-6, p = 0.029) and perceived the medical treatment more negatively (72.1 vs. 79.7, scale 0-100, p = 0.029). Multiple linear regression analysis showed that the variations in HbA1c could be explained by the frequency of bolus doses (p = 0.013) and SMBG per day (p < 0.0001) adjusted for duration and age (r(2) = 0.339, p < 0.0001). CONCLUSION: Insulin omission was common. Those who missed doses were less satisfied and perceived more impact with the treatment. The frequencies of daily boluses and SMBG were associated with metabolic control. Diabetes teams need strategies to guide adolescents on how to avoid insulin omission.

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