| 1. |
- Andersson, Cecilia K, et al.
(författare)
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Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study.
- 2013
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 14:5, s. 341-349
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Benediktsdottir, Berglind E., et al.
(författare)
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Synthesis of N,N,N-trimethyl chitosan homopolymer and highly substituted N-alkyl-N,N-dimethyl chitosan derivatives with the aid of di-tert-butyldimethylsilyl chitosan
- 2011
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 86:4, s. 1451-1460
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Tidskriftsartikel (refereegranskat)abstract
- A highly chemoselective strategy for the synthesis of N,N,N-trimethyl chitosan (TMC) homopolymer and highly substituted N-alkyl-N,N-dimethyl chitosan derivatives was achieved using di-tert-butyldimethylsilyl-3,6-O-chitosan (di-TBDMS chitosan) as a precursor. The influence of different solvents, reagents and other reaction conditions on the reduction, trimethylation and quaternization of these di-TBDMS chitosan derivatives was studied. Products were characterized by NMR after each step. Di-TBDMS chitosan was reacted with methyl iodide in NMP, giving a 100% substituted TMC with the trimethyl group appearing at 3.35 ppm in H-1 NMR spectrum. N-Propyl-, N-butyl- and N-hexyl-N,N-dimethyl chitosan derivatives were synthesized by stepwise reductive alkylation of di-TBDMS chitosan, followed by quaternization with dimethyl sulfate in dichloromethane, giving 65-72% substituted N-alkyl-N,N-dimethyl chitosan derivatives under optimized conditions. Analysis of these water-soluble chitosan derivatives by FT-IR, H-1 NMR, C-13 NMR, H-1-H-1 COSY and H-1-C-13 HSQC NMR enabled detailed structural characterization. All peaks could be assigned to N-modification, showing the selectivity of the di-TBDMS protection. (C) 2011 Elsevier Ltd. All rights reserved.
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| 3. |
- Elding Larsson, Helena, et al.
(författare)
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Safety and efficacy of autoantigen-specific therapy with 2 doses of alum-formulated glutamate decarboxylase in children with multiple islet autoantibodies and risk for type 1 diabetes : A randomized clinical trial
- 2018
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 19:3, s. 410-419
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Treatments have failed to delay or stop the autoimmune process, preceding onset of type 1 diabetes. We investigated if autoantigen-specific treatment with alum-formulated glutamate decarboxylase (GAD-Alum) was safe and affected progression to type 1 diabetes in children with islet autoimmunity.METHODS: In an investigator-initiated, double-blind, placebo-controlled clinical trial, non-diabetic children aged 4 to 17.9 years with autoantibodies to glutamate decarboxylase (GADA) and at least one of insulinoma-associated protein 2, insulin or zinc-transporter 8, were randomized, stratified by 2 or ≥3 islet autoantibodies, to 2 injections of 20 μg GAD-Alum or placebo, 30 days apart. Main outcome was safety, investigated by adverse events, hematology, chemistry, thyroid and celiac autoimmunity and titers of islet autoantibodies, and efficacy, investigated by cumulative incidence of diabetes onset over 5-year follow-up. Secondary variables: change in first-phase insulin release (FPIR) after intravenous glucose tolerance tests, fasting, 120 minutes and Area under the curve (AUC) C-peptide and p-glucose after oral glucose tolerance tests and HbA1c.RESULTS: Fifty children (median age: 5.2) were assigned 1:1 to GAD-Alum or placebo, all receiving full treatment and included in the analyses. GAD-Alum did not affect any safety parameter, while GADA titers increased (P = .001). Time to clinical diagnosis was not affected by treatment (hazard ratio, HR = 0.77, P = .574) in the full population or in the separate stratum groups. Treatment did not affect any of the secondary variables.CONCLUSIONS: GAD-Alum as a subcutaneous prime and boost injection was safe in prediabetic young children but did not affect progression to type 1 diabetes. The safety of GAD-Alum should prove useful in future prevention studies.
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| 4. |
- Johnson, Randi K., et al.
(författare)
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Metabolite-related dietary patterns and the development of islet autoimmunity
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The role of diet in type 1 diabetes development is poorly understood. Metabolites, which reflect dietary response, may help elucidate this role. We explored metabolomics and lipidomics differences between 352 cases of islet autoimmunity (IA) and controls in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. We created dietary patterns reflecting pre-IA metabolite differences between groups and examined their association with IA. Secondary outcomes included IA cases positive for multiple autoantibodies (mAb+). The association of 853 plasma metabolites with outcomes was tested at seroconversion to IA, just prior to seroconversion, and during infancy. Key compounds in enriched metabolite sets were used to create dietary patterns reflecting metabolite composition, which were then tested for association with outcomes in the nested case-control subset and the full TEDDY cohort. Unsaturated phosphatidylcholines, sphingomyelins, phosphatidylethanolamines, glucosylceramides, and phospholipid ethers in infancy were inversely associated with mAb+ risk, while dicarboxylic acids were associated with an increased risk. An infancy dietary pattern representing higher levels of unsaturated phosphatidylcholines and phospholipid ethers, and lower sphingomyelins was protective for mAb+ in the nested case-control study only. Characterization of this high-risk infant metabolomics profile may help shape the future of early diagnosis or prevention efforts. © 2019, The Author(s).
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| 5. |
- Jonsdottir, Berglind, et al.
(författare)
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Are Perinatal Events Risk Factors for Childhood Thyroid Autoimmunity?
- 2017
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Ingår i: European Thyroid Journal. - : Bioscientifica. - 2235-0640 .- 2235-0802. ; 6:6, s. 298-306
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental and genetic factors possibly trigger thyroid autoimmunity. Studies on perinatal risk factors for childhood thyroid autoimmunity are sparse.Objectives: The aim was to investigate if perinatal factors, family history of autoimmune diseases, and HLA-DQ genotypes contribute to thyroid autoimmunity in the Diabetes Prediction in Skåne (DiPiS) study.Methods: Samples from 1,874 ten-year-old children were analyzed for autoantibodies to thyroid peroxidase (TPOAb), thyroglobulin (TGAb), and HLA-DQ genotypes. Information on perinatal events and family history of autoimmunity was gathered prospectively in questionnaires.Results: Thyroid autoimmunity was found in 6.9% of the children (TPOAb 4.4%, TGAb 5.8%, both autoantibodies 3.3%) and was overrepresented in girls. Prematurity was positively related to TGAb (OR: 2.4, p = 0.003, p c = 0.021). Autoimmune diseases in the family increased the risk of thyroid autoimmunity: TPOAb (OR: 2.2, p = 0.012), any autoantibody (OR: 1.7, p = 0.04), and both autoantibodies (OR: 2.2, p = 0.024). A first-degree relative (FDR) with thyroid disease increased the risk for TPOAb (OR: 2.4, p = 0.03) and both autoantibodies (OR: 2.6, p = 0.03), a FDR or sibling with celiac disease increased the risk for both autoantibodies (OR: 3.7, p = 0.03, and OR: 4.8, p = 0.003), a FDR or sibling with diabetes increased the risk for thyroid autoantibody (OR: 3.0, p = 0.01, and OR: 5.4, p = 0.032), and a father with rheumatic disease increased the risk for TPOAb (OR: 15.2, p = 0.017), TGAb (OR: 11.3, p = 0.029), any autoantibody (OR: 9.6, p = 0.038), and both autoantibodies (OR: 20, p = 0.01).Conclusions: Thyroid autoimmunity was found in 6.9% of the 10-year-old children who were being followed for their risk of type 1 diabetes. No relation to perinatal factors was found, with the exception of a possible association between prematurity and TGAb. Family history of autoimmune diseases increased the risk of thyroid autoimmunity.
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| 6. |
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| 7. |
- Jonsdottir, Berglind, et al.
(författare)
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Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study
- 2018
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 228-237
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth. Methods: In 10-year-old children (n = 1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11–16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer’s exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman’s rank correlation test. Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p <.001) also having higher TPOAb levels at 10 years (p =.049). TPOAb was associated with GADA (p =.002), ZnT8R/W/QA (p =.001) and IA-2A (p =.001) while TGAb were associated with ZnT8R/W/QA (p =.021). In boys only, TPOAb were associated with GADA (p =.002), IA-2A (p =.001), ZnT8R/W/QA (p =.001) and IAA (p =.009), and TGAb with GADA (p =.013), IA-2A (p =.005) and ZnT8R/W/QA (p =.003). Levels of IA-2A correlated to both TPOAb (p =.021) and to TGAb (p =.011). In boys only, levels of GADA and TGAb correlated (p =.009 as did levels of IA-2A and TPOAb (p =.013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine. Conclusions: Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity.
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| 8. |
- Jonsdottir, Berglind, et al.
(författare)
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Early appearance of thyroid autoimmunity in children followed from birth for type 1 diabetes risk
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Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197.
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define pre-clinical autoimmune thyroid disease (AITD) which can progress to either clinical hypo- or hyperthyroidism. We determined the age at seroconversion in children genetically at risk for type 1 diabetes.METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Children seropositive on the cross-sectional initial screen at 8-13 years of age had longitudinally collected samples (from 3.5 months of age) screened retrospectively and prospectively for thyroid autoantibodies to identify the age at seroconversion. First-appearing autoantibody was related to sex, HLA genotype, family history of AITD, and subsequent thyroid dysfunction and disease.RESULTS: The youngest appearance of TPOAb and TgAb was 10 and 15 months of age, respectively. Girls had higher incidence rates of both autoantibodies. Family history of AITD was associated with a higher risk of TPOAb hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.17, 3.08; and TgAb HR 2.55, 95% CI 1.91, 3.41. The risk of progressing to hypo- or hyperthyroidism was not different between TgAb and TPOAb, but children with both autoantibodies appearing at the same visit had a higher risk compared to TPOAb appearing first (HR 6.34, 95% CI 2.72, 14.76).MAIN CONCLUSION: Thyroid autoantibodies may appear during the first years of life, especially in girls, and in children with a family history of AITD. Simultaneous appearance of both autoantibodies increases the risk for hypo- or hyperthyroidism.
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| 9. |
- Jonsdottir, Berglind, et al.
(författare)
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Prevalence of diabetes and presence of autoantibodies against zinc transporter 8 and glutamic decarboxylase at diagnosis and at follow up of Graves’ disease
- 2019
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 64:1, s. 48-54
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of this work was to investigate, in patients with newly diagnosed Graves’ disease (GD), the frequency of islet autoantibodies including autoantibodies against Zink transporter 8 (ZnT8A), as well as to investigate the relation between thyroid autoantibodies, islet autoantibodies and diabetes both before GD diagnosis and at follow-up. Methods: Blood samples from 278 patients with newly diagnosed GD were analyzed for autoantibodies against glutamic acid decarboxylase (GADA), insulinoma-associated protein-2 (IA2-A), three variants of zinc transporter 8 (ZnT8A), thyroid peroxidase (TPOA) and the TSH receptor (TRAb). Information on other autoimmune diseases, as well as development of diabetes during follow up was gathered from patient’s medical journal. Results: At GD diagnosis, 13.7% were positive for islet autoantibodies, with the majority being positive for GADA (8.7%) and ZnT8A (7.6%). TPOA were found positive in 71% and TRAb in 83%. No association was found between islet autoantibodies and thyroid autoantibodies or diabetes diagnosis during follow up. Positive association was found between islet autoantibodies and all forms of diabetes, diagnosed both before and after GD (OR: 2.5, CI: 1.1–6.8, p = 0.03) but not to other autoimmune diseases at GD diagnosis. Conclusions: The incidence of GADA and ZnT8A in patients with GD is high and might indicate wide range endocrine autoimmunity, as well as risk for non-autoimmune diabetes rather than exclusively mark beta cell autoimmunity and type 1 diabetes.
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| 10. |
- Jonsdottir, Berglind, et al.
(författare)
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Thyroid and islet autoantibodies predict autoimmune thyroid disease already at Type 1 diabetes diagnosis
- 2017
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 102:4, s. 1277-1285
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Screening of autoimmune thyroid disease in children and young adults with Type 1 diabetes is important but vary greatly between clinics.OBJECTIVE: The aim was to determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA- DQ at diagnosis of Type 1 diabetes for autoimmune thyroid disease during subsequent follow-up.SETTING: 43 Paediatric Endocrinology units Sweden. Design, patients and main outcome measures: At diagnosis of Type 1 diabetes, samples from 2433 children were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), and the three variants of the zinc transporter 8 (ZnT8W/R/QA) as well as HLA-DQA1-B1 genotypes and thyroid function. After 5.1-9.5 years disease duration, children treated with thyroxine were identified in the Swedish National Board of Health and Welfare Prescribed Drug Register.RESULTS: Thyroxine had been prescribed to 6% (147/2433; 66% girls). In patients below 5 years, female gender (HR=4.60, p=0.008) and GADA (HR=5.80, p=0.02) were significant predictors. In patients 5-10 years, TPOAb (HR=20.56, p<0.0001), TGAb (HR=3.40, p=0.006) and TSH outside the reference limit (HR=3.64, p<0.001) were predictors while in the 10-15 year olds, TPOAb (HR=17.00, p<0.001) and TSH outside the reference limit (HR=4.11, p<0.001) predicted future thyroxine prescription.CONCLUSION: In addition to TPOAb and TSH, positive GADA tested at the diagnosis of type 1 diabetes is important for the prediction of autoimmune thyroid disease in children below 5 years of age.
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| 11. |
- 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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| 12. |
- Krischer, Jeffrey P, et al.
(författare)
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Predicting Islet Cell Autoimmunity and Type 1 Diabetes : An 8-Year TEDDY Study Progress Report
- 2019
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 42:6, s. 1051-1060
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Assessment of the predictive power of The Environmental Determinants of Diabetes in the Young (TEDDY)-identified risk factors for islet autoimmunity (IA), the type of autoantibody appearing first, and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: A total of 7,777 children were followed from birth to a median of 9.1 years of age for the development of islet autoantibodies and progression to T1D. Time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves were calculated to provide estimates of their individual and collective ability to predict IA and T1D.RESULTS: HLA genotype (DR3/4 vs. others) was the best predictor for IA (Youden's index J = 0.117) and single nucleotide polymorphism rs2476601, in PTPN22, was the best predictor for insulin autoantibodies (IAA) appearing first (IAA-first) (J = 0.123). For GAD autoantibodies (GADA)-first, weight at 1 year was the best predictor (J = 0.114). In a multivariate model, the area under the ROC curve (AUC) was 0.678 (95% CI 0.655, 0.701), 0.707 (95% CI 0.676, 0.739), and 0.686 (95% CI 0.651, 0.722) for IA, IAA-first, and GADA-first, respectively, at 6 years. The AUC of the prediction model for T1D at 3 years after the appearance of multiple autoantibodies reached 0.706 (95% CI 0.649, 0.762).CONCLUSIONS: Prediction modeling statistics are valuable tools, when applied in a time-until-event setting, to evaluate the ability of risk factors to discriminate between those who will and those who will not get disease. Although significantly associated with IA and T1D, the TEDDY risk factors individually contribute little to prediction. However, in combination, these factors increased IA and T1D prediction substantially.
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| 13. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 14. |
- Lundgren, Markus, et al.
(författare)
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Effect of screening for type 1 diabetes on early metabolic control : the DiPiS study
- 2019
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 62:1, s. 53-57
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: It has been shown that children previously enrolled in follow-up studies have better glycaemic control during the early period after diabetes diagnosis. The aim of this study was to analyse glycaemic control over a longer period, past the period of partial remission, after diagnosis in children followed before diagnosis in the Swedish Diabetes Prediction in Skåne (DiPiS) study compared with children of equal age not enrolled in pre-diabetes follow-up, receiving equivalent diabetes care. Methods: HbA1c from diagnosis and for the following 5 years, as well as differences in insulin dosage, BMI, pump use, partial remission according to insulin dose-adjusted HbA1c and baseline demographics were compared between children who were enrolled in follow-up and had received information on diabetes risk (n = 51) and children not enrolled in follow-up (n = 78). Results: The group followed before diagnosis had a higher proportion of first-degree relatives (FDRs) with diabetes (28% vs 5.6%; p = 0.001) and a higher proportion of participants with mothers born in Sweden (100% vs 89%; p = 0.02). No significant differences in total daily insulin dose, pump use or other baseline sociodemographic factors were detected between the groups. Median HbA1c at diagnosis and at 1, 2, 3, 4 and 5 years after diabetes diagnosis was significantly lower in children followed before diagnosis (all p < 0.05), and was not related to FDR status. Conclusions/interpretation: Compared with controls not previously enrolled in follow-up, our study shows that children enrolled in longitudinal follow-up before the diagnosis of diabetes have better glycaemic control, measured by HbA1c, up to 5 years after diagnosis and during the initial period of partial remission. Improved glycaemic control in the initial years of living with type 1 diabetes could affect long-term outcome and complications and might also improve study enrolment in future longitudinal studies.
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| 15. |
- Smith, Laura B., et al.
(författare)
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Psychological manifestations of celiac disease autoimmunity in young children
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 139:3
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Psychological symptoms can be associated with celiac disease; abstract however, this association has not been studied prospectively in a pediatric cohort. We examined mother report of psychological functioning in children persistently positive for tissue transglutaminase autoantibodies (tTGA), defined as celiac disease autoimmunity (CDA), compared with children without CDA in a screening population of genetically at-risk children. We also investigated differences in psychological symptoms based on mothers' awareness of their child's CDA status. METHODS: The Environmental Determinants of Diabetes in the Young study followed 8676 children to identify triggers of type 1 diabetes and celiac disease. Children were tested for tTGA beginning at 2 years of age. The Achenbach Child Behavior Checklist assessed child psychological functioning at 3.5 and 4.5 years of age. RESULTS: At 3.5 years, 66 mothers unaware their child had CDA reported more child anxiety and depression, aggressive behavior, and sleep problems than 3651 mothers of children without CDA (all Ps ≤ .03). Unaware-CDA mothers also reported more child anxiety and depression, withdrawn behavior, aggressive behavior, and sleep problems than 440 mothers aware of their child's CDA status (all Ps ≤.04). At 4.5 years, there were no differences. CONCLUSIONS: In 3.5-year-old children, CDA is associated with increased reports of child depression and anxiety, aggressive behavior, and sleep problems when mothers are unaware of their child's CDA status. Mothers' knowledge of their child's CDA status is associated with fewer reports of psychological symptoms, suggesting that awareness of the child's tTGA test results affects reporting of symptoms.
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| 16. |
- Törn, Carina, et al.
(författare)
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Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- A total of 15 SNPs within complement genes and present on the ImmunoChip were analyzed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. A total of 5474 subjects were followed from three months of age until islet autoimmunity (IA: n = 413) and the subsequent onset of type 1 diabetes (n = 115) for a median of 73 months (IQR 54-91). Three SNPs within ITGAM were nominally associated (p < 0.05) with IA: rs1143678 [Hazard ratio; HR 0.80; 95% CI 0.66-0.98; p = 0.032], rs1143683 [HR 0.80; 95% CI 0.65-0.98; p = 0.030] and rs4597342 [HR 1.16; 95% CI 1.01-1.32; p = 0.041]. When type 1 diabetes was the outcome, in DR3/4 subjects, there was nominal significance for two SNPs: rs17615 in CD21 [HR 1.52; 95% CI 1.05-2.20; p = 0.025] and rs4844573 in C4BPA [HR 0.63; 95% CI 0.43-0.92; p = 0.017]. Among DR4/4 subjects, rs2230199 in C3 was significantly associated [HR 3.20; 95% CI 1.75-5.85; p = 0.0002, uncorrected] a significance that withstood Bonferroni correction since it was less than 0.000833 (0.05/60) in the HLA-specific analyses. SNPs within the complement genes may contribute to IA, the first step to type 1 diabetes, with at least one SNP in C3 significantly associated with clinically diagnosed type 1 diabetes.
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