| 1. |
- Andersson Svärd, Agnes, et al.
(författare)
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Characterization of plasma lipidomics in adolescent subjects with increased risk for type 1 diabetes in the DiPiS cohort
- 2020
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Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Type 1 diabetes (T1D) is caused by the destruction of pancreatic islet beta cells resulting in total loss of insulin production. Recent studies have suggested that the destruction may be interrelated to plasma lipids.OBJECTIVES: Specific lipids have previously been shown to be decreased in children who develop T1D before four years of age. Disturbances of plasma lipids prior to clinical diagnosis of diabetes, if true, may provide a novel way to improve prediction, and monitor disease progression.METHODS: A lipidomic approach was utilized to analyze plasma from 67 healthy adolescent subjects (10-15 years of age) with or without islet autoantibodies but all with increased genetic risk for T1D. The study subjects were enrolled at birth in the Diabetes Prediction in Skåne (DiPiS) study and after 10-15 years of follow-up we performed the present cross-sectional analysis. HLA-DRB345, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genotypes were determined using next generation sequencing. Lipidomic profiles were determined using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Lipidomics data were analyzed according to genotype.RESULTS: Variation in levels of several specific phospholipid species were related to level of autoimmunity but not development of T1D. Five glycosylated ceramides were increased in insulin autoantibody (IAA) positive adolescent subjects compared to adolescent subjects without this autoantibody. Additionally, HLA genotypes seemed to influence levels of long chain triacylglycerol (TG).CONCLUSION: Lipidomic profiling of adolescent subjects in high risk of T1D may improve sub-phenotyping in this high risk population.
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| 2. |
- Mansachs, Sara Juul, et al.
(författare)
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Genetic Variants Associated with Neuropeptide Y Autoantibody Levels in Newly Diagnosed Individuals with Type 1 Diabetes
- 2022
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Ingår i: Genes. - : MDPI AG. - 2073-4425. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- (1) Autoantibodies to the leucine variant of neuropeptide Y (NPY-LA) have been found in individuals with type 1 diabetes (T1D). We investigated the association between the levels of NPY-LA and single nucleotide polymorphisms (SNP) to better understand the genetic regulatory mechanisms of autoimmunity in T1D and the functional impacts of increased NPY-LA levels. (2) NPY-LA measurements from serum and SNP genotyping were done on 560 newly diagnosed individuals with T1D. SNP imputation with the 1000 Genomes reference panel was followed by an association analysis between the SNPs and measured NPY-LA levels. Additionally, functional enrichment and pathway analyses were done. (3) Three loci (DGKH, DCAF5, and LINC02261) were associated with NPY-LA levels (p-value < 1.5 × 10−6), which indicates an association with neurologic and vascular disorders. SNPs associated with variations in expression levels were found in six genes (including DCAF5). The pathway analysis showed that NPY-LA was associated with changes in gene tran-scription, protein modification, immunological functions, and the MAPK pathway. (4) Conclu-sively, we found NPY-LA to be significantly associated with three loci (DGKH, DCAF5, and LINC02261), and based on our findings we hypothesize that the presence of NPY-LA is associated with the regulation of the immune system and possibly neurologic and vascular disorders.
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| 3. |
- Thorsen, Steffen U, et al.
(författare)
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Interaction Between Dietary Iron Intake and Genetically Determined Iron Overload : Risk of Islet Autoimmunity and Progression to Type 1 Diabetes in the TEDDY Study
- 2023
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 46:5, s. 1014-1018
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine whether iron intake and genetically determined iron overload interact in predisposing to the development of childhood islet autoimmunity (IA) and type 1 diabetes (T1D).RESEARCH DESIGN AND METHODS: In The Environmental Determinants of Diabetes in the Young (TEDDY) study, 7,770 genetically high-risk children were followed from birth until the development of IA and progression to T1D. Exposures included energy-adjusted iron intake in the first 3 years of life and a genetic risk score (GRS) for increased circulating iron.RESULTS: We found a U-shaped association between iron intake and risk of GAD antibody as the first autoantibody. In children with GRS ≥2 iron risk alleles, high iron intake was associated with an increased risk of IA, with insulin as first autoantibody (adjusted hazard ratio 1.71 [95% CI 1.14; 2.58]) compared with moderate iron intake.CONCLUSIONS: Iron intake may alter the risk of IA in children with high-risk HLA haplogenotypes.
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