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Measurements of suitably selected serum markers could potentially provide a non-invasive and easily applicable solution to this challenge. Accordingly, we evaluated a broad panel of proteins previously associated with type 1 diabetes in serum from newly diagnosed individuals during the first year from diagnosis. To uncover associations with beta cell function, comparisons were made between these targeted proteomics measurements and changes in fasting C-peptide levels. To further distinguish proteins linked with the disease status, comparisons were made with measurements of the protein targets in age- and sex-matched autoantibody-negative unaffected family members (UFMs).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Selected reaction monitoring (SRM) mass spectrometry analyses of serum, targeting 85 type 1 diabetes-associated proteins, were made. Sera from individuals diagnosed under 18 years (<jats:italic>n<\/jats:italic>=86) were drawn within 6 weeks of diagnosis and at 3, 6 and 12 months afterwards (288 samples in total). The SRM data were compared with fasting C-peptide\/glucose data, which was interpreted as a measure of beta cell function. The protein data were further compared with cross-sectional SRM measurements from UFMs (<jats:italic>n<\/jats:italic>=194).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Eleven proteins had statistically significant associations with fasting C-peptide\/glucose. Of these, apolipoprotein L1 and glutathione peroxidase 3 (GPX3) displayed the strongest positive and inverse associations, respectively. Changes in GPX3 levels during the first year after diagnosis indicated future fasting C-peptide\/glucose levels. In addition, differences in the levels of 13 proteins were observed between the individuals with type 1 diabetes and the matched UFMs. These included GPX3, transthyretin, prothrombin, apolipoprotein C1 and members of the IGF family.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>The association of several targeted proteins with fasting C-peptide\/glucose levels in the first year after diagnosis suggests their connection with the underlying changes accompanying alterations in beta cell function in type 1 diabetes. Moreover, the direction of change in GPX3 during the first year was indicative of subsequent fasting C-peptide\/glucose levels, and supports further investigation of this and other serum protein measurements in future studies of beta cell function in type 1 diabetes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-023-05974-9","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T03:26:02Z","timestamp":1691119562000},"page":"1983-1996","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Targeted serum proteomics of longitudinal samples from newly diagnosed youth with type 1 diabetes distinguishes markers of disease and C-peptide trajectory"],"prefix":"10.1007","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4742-0566","authenticated-orcid":false,"given":"Robert","family":"Moulder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6046-1920","authenticated-orcid":false,"given":"Tommi","family":"V\u00e4likangas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1575-9725","authenticated-orcid":false,"given":"M. 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Qureshi, for their contributions to the management of the samples. Similarly, at Turku Bioscience, M. Hakkarainen and S. Heinonen are thanked for their excellent technical assistance, and likewise the Turku Bioscience Proteomics core facility, supported by the University of Turku, \u00c5bo Akademi University and Biocenter Finland. The full list of INNODIA consortium members is shown below. Figure  and the graphical abstract were created using BioRender.com.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Access to these person-sensitive data is only through secure environments and by application to the INNODIA Data Access Committee.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 115797 (INNODIA) and No. 945268 (INNODIA HARVEST). This Joint Undertaking receives support from the Union\u2019s Horizon 2020 research and innovation programme, \u2018EFPIA\u2019, \u2018JDRF\u2019 and \u2018The Leona M. and Harry B. Helmsley Charitable Trust\u2019. RL received funding from the Academy of Finland (grants 292335, 294337, 319280, 31444, 319280, 329277, 331790), from Business Finland and by grants from JDRF, the Sigrid Jus\u00e9lius Foundation, the Jane and Aatos Erkko Foundation, the Finnish Diabetes Foundation and the Finnish Cancer Foundation. LLE reports grants from the European Research Council (ERC) (677943), the Academy of Finland (310561, 314443, 329278, 335434, 335611 and 341342) and the Sigrid Jus\u00e9lius Foundation during the conduct of the study. RL and MK were supported by the Academy of Finland, AoF, Centre of Excellence in Molecular Systems Immunology and Physiology Research (2012\u20132017, grants 250114 and 292482). MK also received support from the Sigrid Jus\u00e9lius Foundation, Helsinki University Hospital Research Funds and the Liv and H\u00e4lsa Fund. Research at Turku Bioscience Centre (LLE and RL) was supported by the University of Turku Graduate School (UTUGS), Biocenter Finland, ELIXIR Finland and by the InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530). TV is supported by the Doctoral Programme in Mathematics and Computer Sciences (MATTI) of the University of Turku. MKH was supported by the Turku Doctoral Programme of Molecular Medicine (TuDMM), the Finnish Cultural Foundation and the Finnish Diabetes Research Foundation.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"SB has ownerships in Intomics A\/S, Hoba Therapeutics Aps, Novo Nordisk A\/S, Lundbeck A\/S, ALK abello A\/S and managing board memberships in Proscion A\/S and Intomics A\/S. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"RM conducted the analyses, prepared tables and figures, interpreted the data and co-wrote the manuscript. TV analysed and interpreted the data, prepared the tables and figures, and co-wrote the manuscript. MKH analysed, evaluated and interpreted the data; prepared the figures; and co-wrote the manuscript. TS supervised the analysis of the data. CAB processed and prepared the data. LO, NL and SB participated in the design of the study. DBD, MP, PJC, SB, AMS and CM initiated, designed and supervised the study. MK, LLE and RL designed and supervised the study. With the unavoidable exception of DBD (deceased), all authors edited, reviewed and approved the final version of the manuscript. RL is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}},{"value":"Mathieu C, Gillard P, Casteels K, Overbergh L (KU Leuven, Belgium), Dunger D, Wallace C, Evans M, Thankamony A, Hendriks E, Bruggraber S, Qureshi A, Marcovecchio L, Paediatrics laboratory staff (University of Cambridge, UK), Peakman M, Tree T (King\u2019s College London, UK), Morgan N, Richardson S (University of Exeter, UK), Todd J, Wicker L (University of Oxford, UK), Mander A, Dayan C, Alhadj Ali M (Cardiff University, UK), Pieber T (Medical University of Graz, Austria), Eizirik D, Cnop M (Universite Libre de Bruxelles, Belgium), Brunak S (University of Copenhagen, Denmark), Pociot F, Johannesen J, Rossing P, Legido Quigley C (Herlev University Hospital, Region Hovedstaden, Denmark), Mallone R, Scharfmann R, Boitard C (Cochin Institute Paris, France), Knip M, Otonkoski T (University of Helsinki, Finland), Veijola R (University of Oulu, Finland), Lahesmaa R, Oresic M, Toppari J (University of Turku, Finland), Danne T (Children's and Youth Hospital Hannover, Germany), Ziegler AG, Achenbach P, Rodriguez-Calvo T (Helmholtz Zentrum Muenchen, Germany), Solimena M, Bonifacio E, Speier S (TU Dresden, Germany), Holl R (University of Ulm, Germany), Dotta F (University of Siena, Italy), Chiarelli F (University of Chieti, Italy), Marchetti P (University of Pisa, Italy), Bosi E (University Vita-Salute San Raffaele, Italy), Cianfarani S, Ciampalini P (Bambino Ges\u00f9 Children's Hospital, Italy), de Beaufort C (Centre Hospitalier de Luxembourg, Luxemburg), Dahl-J\u00f8rgensen K, Skrivarhaug T, Joner G, Krogvold L (Oslo University Hospital, Norway), Jarosz-Chobot P (Medical University of Silesia, Poland), Battelino T (University of Ljubljana, Slovenia), Thorens B (University of Lausanne, Switzerland), Gotthardt M (Radboud University Medical Center, the Netherlands), Roep B, Nikolic T, Zaldumbide A (Leiden University Medical Center, the Netherlands), Lernmark A, Lundgren M (Lund University, Sweden), Costecalde G (Univercell-Biosolutions, France), Strube T, Schulte A, Nitsche A, (Sanofi, Germany), Peakman M, Vela J (Sanofi, United States), von Herrath M, Wesley J, (Novo Nordisk, Denmark), Napolitano-Rosen A (GlaxoSmithKline, UK), Thomas M, Schloot N (Eli Lilly, UK), Goldfine A, Waldron-Lynch F, Kompa J, Vedala A, Hartmann N, Nicolas G (Novartis Pharma AG, Switzerland), van Rampelbergh J, Bovy N (Imcyse SA, Belgium), Dutta S, Soderberg J, Ahmed S, Martin F, Latres E (JDRF, USA), Agiostratidou G, Koralova A (The Leona M. and Harry B. Helmsley Charitable Trust, USA).","order":6,"name":"Ethics","group":{"name":"EthicsHeading","label":"Members of the INNODIA and INNODIA HARVEST consortia"}},{"value":"Willemsen R (Barts Health NHS Trust, UK), Smith A (Northampton General Hospital NHS Trust, UK), Anand B (West Suffolk NHS FT, UK), Puthi V (North West Anglia NHS FT, UK), Zac-Varghese S (East & North Hertfordshire NHS Trust, UK), Datta V (Norfolk & Norwich University NHS FT, UK), Dias R (Birmingham Women\u2019s and Children\u2019s NHS FT, UK), Sundaram P (University Hospitals of Leicester NHS Trust, UK), Vaidya B (Royal Devon & Exeter NHS FT, UK), Patterson C (NHS Fife, UK), Owen K (Oxford University Hospitals NHS FT, UK), Dayan C (Cardiff & Vale University Health Board, UK), Piel B (Queen Elizabeth Hospital, King\u2019s Lynn FT, UK), Heller S (Sheffield Teaching Hospitals NHS FT, UK), Randell T, Gazis T (Nottingham University Hospitals NHS Trust, UK), Bismuth Reismen E, Carel J-C (Hospital Robert Debre, France), Riveline J-P, Gautier J-F (Hospital Lariboisiere, France), Andreelli F (Hospital Lapitie-Salpetriere, France), Travert F (Hospital Bichat Claude Bernard, France), Cosson E (Hospital Jean-Verdier, France), Penfornis A, Petit C (Centre Hospitalier Sud-Francilien, France), Feve B (Hospital St Antoine, France), Lucidarme N (Hospital Jean-Verdier Pediatrie, France), Cosson E (Hospital Avicenne, France), Beressi J-P (Hospital Andre Mignot, France), Ajzenman C (Hospital Andre Mignot Pediatrie, France), Radu A (Hospital Europeen Georges-Pompidou, France), Greteau-Hamoumou S (Hospital Louis Mourier, France), Bibal C (Hospital Kremlin Bicetre, France), Meissner T (Universitatsklinikum der Heinrich-Heine-Univeritat Dusseldorf, Germany), Heidtmann B (Katholisches Kinderkrankenhaus Wilhelmstift, Germany), Toni S (AOU Meyer, Italy), Rami-Merhar B (Medical University of Vienna, Austria), Eeckhout B, Peene B, Vantongerloo N (Algemeen Ziekenhuis Geel Sint-Dimpna Geel, Belgium), Maes T, Gommers L (Imeldziekenhuis Bonheiden, Belgium).","order":7,"name":"Ethics","group":{"name":"EthicsHeading","label":"Associated clinical sites"}}]}}