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- Jonsdottir, Berglind, et al.
(författare)
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Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents
- 2013
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Ingår i: Diabetologia. - : Springer Verlag (Germany). - 0012-186X .- 1432-0428. ; 56:8, s. 1735-1742
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to investigate, in children newly diagnosed with type 1 diabetes: (1) the prevalence of autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TGAb); and (2) the association between TPOAb, TGAb or both, with either islet autoantibodies or HLA-DQ genes. less thanbrgreater than less thanbrgreater thanBlood samples from 2,433 children newly diagnosed with type 1 diabetes were analysed for TPOAb and TGAb in addition to autoantibodies against arginine zinc transporter 8 (ZnT8RA), tryptophan zinc transporter 8 (ZnT8WA), glutamine zinc transporter 8 (ZnT8QA), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), HLA-DQA-B1 genotypes, thyroid-stimulating hormone (TSH) and free thyroxine (T4). less thanbrgreater than less thanbrgreater thanAt type 1 diabetes diagnosis, 12% of the children had thyroid autoantibodies (60% were girls; p andlt; 0.0001). GADA was positively associated with TPOAb (p andlt; 0.001) and with TGAb (p andlt; 0.001). In addition, ZnT8A was associated with both TPOAb (p = 0.039) and TGAb (p = 0.015). DQB1*05:01 in any genotype was negatively associated with TPOAb (OR 0.55, 95% CI 0.37, 0.83, p value corrected for multiple comparisons (p (c)) = 0.012) and possibly with TGAb (OR 0.55, 95% CI 0.35, 0.87, p (c) = 0.07). Thyroid autoimmunity in children newly diagnosed with type 1 diabetes was rarely (0.45%) associated with onset of clinical thyroid disease based on TSH and free T4. less thanbrgreater than less thanbrgreater thanGADA and ZnT8A increased the risk for thyroid autoimmunity at the time of clinical diagnosis of type 1 diabetes, while HLA-DQB1*05:01 reduced the risk. However, the associations between thyroid autoimmunity and HLA-DQ genotype were weak and did not fully explain the co-occurrence of islet and thyroid autoimmunity.
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- Ludvigsson, Johnny, et al.
(författare)
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Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial
- 2011
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Ingår i: DIABETOLOGIA. - : Springer Science Business Media. - 0012-186X .- 1432-0428. ; 54:3, s. 634-640
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 mu g of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with andlt; 6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 +/- 0.032 nmol/l at day 1 and 0.215 +/- 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 +/- 0.039 and 0.184 +/- 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. ClinicalTrials.gov NCT00435981 The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.
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- Svensson, Matilda1, et al.
(författare)
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Antibodies to Influenza Virus A/H1N1 Hemagglutinin in Type 1 Diabetes Children Diagnosed Before, During and After the SWEDISH A(H1N1)pdm09 Vaccination Campaign 2009-2010
- 2014
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 79:2, s. 137-148
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Tidskriftsartikel (refereegranskat)abstract
- We determined A/H1N1-hemagglutinin (HA) antibodies in relation to HLAD-Q genotypes and islet autoantibodies at clinical diagnosis in 1141 incident 0.7 to 18-year-old type 1 diabetes patients diagnosed April 2009-December 2010. Antibodies to S-35-methionine-labelled A/H1N1 hemagglutinin were determined in a radio-binding assay in patients diagnosed before (n = 325), during (n = 355) and after (n = 461) the October 2009-March 2010 Swedish A(H1N1) pdm09 vaccination campaign, along with HLA-DQ genotypes and autoantibodies against GAD, insulin, IA-2 and ZnT8 transporter. Before vaccination, 0.6% patients had A/H1N1-HA antibodies compared with 40% during and 27% after vaccination (P less than 0.0001). In children less than3 years of age, A/H1N1-HA antibodies were found only during vaccination. The frequency of A/H1N1-HA antibodies during vaccination decreased after vaccination among the 3 less than 6 (P = 0.006) and 13 less than 18 (P = 0.001), but not among the 6 less than 13-year-olds. HLA-DQ2/8 positive children less than3 years decreased from 54% (15/28) before and 68% (19/28) during, to 30% (9/30) after vaccination (P = 0.014). Regardless of age, DQ2/2; 2/X (n = 177) patients had lower frequency (P = 0.020) and levels (P = 0.042) of A/H1N1-HA antibodies compared with non-DQ2/2; 2/X (n = 964) patients. GADA frequency was 50% before, 60% during and 51% after vaccination (P = 0.009). ZnT8QA frequency increased from 30% before to 34% during and 41% after vaccination (P = 0.002). Our findings suggest that young (less than3 years) along with DQ2/2; 2/X patients were low responders to Pandemrix (R). As the proportion of DQ2/8 patients less than3 years of age decreased after vaccination and the frequencies of GADA and ZnT8QA were enhanced, it cannot be excluded that the vaccine affected clinical onset of type 1 diabetes.
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