Koskinen, Maarit K.Helminen, OlliMatomaki, JaakkoAspholm, SusannaMykkanen, JuhaMakinen, MarjaanaSimell, VilleVaha-Makila, MariSimell, TuulaIlonen, JormaKnip, MikaelVeijola, RiittaToppari, JormaSimell, Olli2016-03-182016-03-182016-03Koskinen, M K, Helminen, O, Matomaki, J, Aspholm, S, Mykkanen, J, Makinen, M, Simell, V, Vaha-Makila, M, Simell, T, Ilonen, J, Knip, M, Veijola, R, Toppari, J & Simell, O 2016, 'Reduced beta-cell function in early preclinical type 1 diabetes', European Journal of Endocrinology, vol. 174, no. 3, pp. 251-259. https://doi.org/10.1530/EJE-15-0674http://hdl.handle.net/10138/160823Objective: We aimed to characterize insulin responses to i.v. glucose during the preclinical period of type 1 diabetes starting from the emergence of islet autoimmunity. Design and methods: A large population-based cohort of children with HLA-conferred susceptibility to type 1 diabetes was observed from birth. During regular follow-up visits islet autoantibodies were analysed. We compared markers of glucose metabolism in sequential intravenous glucose tolerance tests between 210 children who were positive for multiple (>= 2) islet autoantibodies and progressed to type 1 diabetes (progressors) and 192 children testing positive for classical islet-cell antibodies only and remained healthy (non-progressors). Results: In the progressors, the first phase insulin response (FPIR) was decreased as early as 4-6 years before the diagnosis when compared to the non-progressors (P=0.001). The difference in FPIR between the progressors and non-progressors was significant (P Conclusions: FPIR is decreased several years before the diagnosis of type 1 diabetes, implying an intrinsic defect in beta-cell mass and/or function.9enginfo:eu-repo/semantics/openAccess1ST-PHASE INSULIN-RESPONSEINTRAVENOUS GLUCOSEGENERAL-POPULATIONCHILDRENRISKAUTOANTIBODIESSECRETIONANTIBODYPREDICTIONRELATIVESGeneral medicine, internal medicine and other clinical medicineArticleopenAccess582d57b6-a5d7-4976-9392-0291082b83b084958292367000370876800005