Dataset Information

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes

ABSTRACT: Aims/hypothesis: Biomarkers are needed to accurately predict and monitor type 1 diabetes progression during the substantially heterogeneous presymptomatic period of the disease development. To address this concern, we studied temporal changes in the plasma and serum proteomes of < 5-year-old children with HLA-conferred risk for type 1 diabetes, by analysing longitudinal sample series that were collected at regular intervals between birth and diagnosis. Methods: Using mass spectrometry-based discovery proteomics, longitudinal sample series from children positive for multiple autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n=10) were analysed and compared with similar measurements from children, matched from age and gender who were either positive for single autoantibody (n=10) or autoantibody negative (n=10). Following analysis of the data with an additive Gaussian process regression model (LonGP), targeted proteomics was used to verify 11 biomarker candidates in a similar yet independent cohort of children who progressed to the disease within 5 years of age (n=31) and matched autoantibody negative children (n=31). Results: These data reiterated extensive age related trends for protein levels in young children. Further, by combining the utility of LonGP together with the targeted analysis in an extended cohort with more frequent sampling points, these analysis demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first islet autoantibody and remained relatively less abundant in children who later progressed to type 1 diabetes, in comparison to autoantibody negative children. Conclusions/interpretation: Through the comparative analysis of prospectively collected samples, our data indicate that the serum/plasma levels of APOC1 are decreased in islet autoantibody positive children who develop type 1 diabetes at a young age. In future studies, APOC1 could be used as an additional measurement to improve early prediction of type 1 diabetes and selection of subjects for intervention studies.

ORGANISM(S): Homo Sapiens

SUBMITTER: Robert Moulder

PROVIDER: PXD033946 | panorama | Mon Oct 02 00:00:00 BST 2023

REPOSITORIES: PanoramaPublic

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Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes.

Hirvonen M Karoliina MK Lietzén Niina N Moulder Robert R Bhosale Santosh D SD Koskenniemi Jaakko J Vähä-Mäkilä Mari M Nurmio Mirja M Orešič Matej M Ilonen Jorma J Toppari Jorma J Veijola Riitta R Hyöty Heikki H Lähdesmäki Harri H Knip Mikael M Cheng Lu L Lahesmaa Riitta R

Scientific reports 20230924 1

Better understanding of the early events in the development of type 1 diabetes is needed to improve prediction and monitoring of the disease progression during the substantially heterogeneous presymptomatic period of the beta cell damaging process. To address this concern, we used mass spectrometry-based proteomics to analyse longitudinal pre-onset plasma sample series from children positive for multiple islet autoantibodies who had rapidly progressed to type 1 diabetes before 4 years of age (n ...[more]

PMID: 37743383

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Project description:The Environmental Determinants of Diabetes in the Young (TEDDY) Study investigates genetic and genetic-environmental interactions, including gestational events, childhood infections, dietary exposures, and other environmental factors after birth, in relation to the development of islet autoimmunity and type 1 diabetes (T1D). A consortium of six clinical centers assembled to participate in the development and implementation of the study to identify environmental triggers for the development of islet autoimmunity and T1D in genetically susceptible individuals. Beginning in 2004, the TEDDY study screened over 400,000 newborns for high-risk HLA-DR, DQ genotypes from both the general population and families already affected by T1D. The TEDDY study enrolled around 8,676 participants across six clinical centers worldwide (Finland, Germany, Sweden and three in the United States) in the 15-year prospective follow-up. Participants are followed every three months for islet autoantibody (IA) measurements with blood sampling until four years of age and then at least every six months until the age of 15. After the age of four, autoantibody positive participants continue to be followed at three month intervals and autoantibody negative participants are followed at six-month intervals. In addition to the analysis of autoantibodies, additional data and sample collection are performed at each visit. Parents collect monthly stool samples in early childhood. The parents also fill out questionnaires at regular intervals in connection with study visits and record information about diet and health status in the child's TEDDY Book between visits. Continued long-term follow-up of the currently active TEDDY participants will provide important scientific information on early childhood diet, reported and measured infections, vaccinations, and psychosocial stressors that may contribute to the development of type 1 diabetes and islet autoimmunity. Additional information on the TEDDY study is available in the following articles: The Environmental Determinants of Diabetes in the Young (TEDDY) Study. TEDDY Study Group. Annals of the New York Academy of Science, 2008 and TEDDY - The Environmental Determinants of Diabetes in the Young - An Observational Clinical Trial. Annals of the New York Academy of Science, 2006 <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=19120261">Annals of the New York Academy of Science, 2008</a> and TEDDY - The Environmental Determinants of Diabetes in the Young - An Observational Clinical Trial. <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=17130573">Annals of the New York Academy of Science, 2006</a> Details of the TEDDY protocol can be found in The Environmental Determinants of Diabetes in the Young (TEDDY): Genetic Criteria and International Diabetes Risk Screening of 421,000 infants. <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=21564455">Pediatric Diabetes, 2011</a> There are three substudies associated with the current TEDDY project release in dbGaP: <ul> <li>TEDDY SNP Array - <a href="study.cgi?study_id=phs001037">phs001037</a> with targeted SNP array data.</li> <li>TEDDY Microbiome - <a href="study.cgi?study_id=phs001443">phs001443</a> with metagenomic and 16S rRNA sequencing data.</li> <li>TEDDY Gene Expression - <a href="study.cgi?study_id=phs001562">phs001562</a> with gene expression data.</li> </ul>

Dataset Information

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes

Publications

Serum APOC1 levels are decreased in young autoantibody positive children who rapidly progress to type 1 diabetes.

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